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Rahim SA, Bakhsheshi-Rad HR, Licavoli J, Jonard BW, Drelich JW. Overview of biodegradable materials for bone repair and osteosarcoma treatment: From bulk to scaffolds. BIOMATERIALS ADVANCES 2025; 174:214317. [PMID: 40239432 DOI: 10.1016/j.bioadv.2025.214317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 04/18/2025]
Abstract
Osteosarcoma, the most common type of malignant bone tumor that affects growing bones in teenagers and children, has become a significant challenge for medical science. The combination of chemotherapy and surgery has been the standard treatment strategy for decades. However, concerns about tumor recurrence and the toxic effects of the drugs continue to drive materials scientists to develop multifunctional scaffolds that can simultaneously support bone regeneration and prevent tumor recurrence. Emergent multifunctional scaffolds have the potential to foster essential and dynamic cellular communication, which can directly target, signal, stimulate, and enhance the body's natural bone repair response. This review emphasizes the mechanisms involved and highlights various technologies and manufacturing processes that align with the capability of these scaffolds to effectively promote bone repair, especially in the presence of osteosarcoma. Additionally, the review summarizes the current state of knowledge regarding scaffolds based on magnesium (Mg), zinc (Zn), and iron (Fe), as well as the antitumor properties of their corrosion products. The review also discusses the therapeutic potential of Mg-, Zn-, and Fe-based materials in inhibiting osteosarcoma cell proliferation. The article elaborates on the main research challenges and prospects of biodegradable materials for bone repair and osteosarcoma treatment.
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Affiliation(s)
- Shebeer A Rahim
- Department of Materials Science and Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.
| | - Hamid R Bakhsheshi-Rad
- Department of Materials Science and Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA; Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran
| | - Joseph Licavoli
- Department of Materials Science and Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA
| | - Brandon W Jonard
- Department of Orthopedic Surgery, University Hospitals/Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Jaroslaw W Drelich
- Department of Materials Science and Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.
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Daniel JB, Martín-Tereso J. Review: Homeostatic boundaries to dietary Zn, Cu and Mn supply in cattle. Animal 2025; 19:101532. [PMID: 40409160 DOI: 10.1016/j.animal.2025.101532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 04/17/2025] [Accepted: 04/18/2025] [Indexed: 05/25/2025] Open
Abstract
Zinc, Cu, and Mn are critical to sustain animal physiology, and therefore, dietary supplementation to domestic cattle is common practice. However, recent evidence rises concerns about current supplementation levels, as they may exceed dietary tolerance for these nutrients, impairing health and productivity. This generous supplementation has been justified to mitigate the uncertainty in basal mineral supply and its availability. Furthermore, current dietary reference recommendations assume conservative and fixed absorption coefficients. This mathematical simplification greatly limits our ability to precisely define supplemental levels. Apparent absorption efficiency, which comprises absorption and endogenous excretions, is the main mechanism animals use as homeostatic adaptation to a variable dietary supply. The first part of this review summarises quantitative evidence illustrating homeostatic competence of cattle to adapt apparent absorption efficiency, demonstrating a much greater than assumed resilience to low dietary supply. Also, adaptations to high dietary supply are described. These homeostatic adaptations are complex and nutrient-specific, but in all cases, they are tightly orchestrated by the animal's trace metal status, sharply increasing nutritional efficiency when status is low and decreasing it under abundant supply. Identifying the lower and upper boundaries of this homeostatic competence serves much better to prevent dietary deficiencies and excess in trace metal supply by supplementation. The second part of this review is therefore dedicated to estimating the lower boundaries of homeostasis defined as the maximal apparent absorption efficiency that can be achieved under constrained dietary availability. Among the three trace minerals evaluated, Cu and Mn supplies appear the most susceptible to nutritional challenge, despite adaptive upregulation of apparent absorption. Finally, the third and last part of the review intends to identify the upper boundaries of dietary trace metal regulation, that is, the supply levels above which homeostasis is overwhelmed resulting in unregulated trace metal retention. Dry matter intake plays a critical role in this risk, specifically in dairy cows. Indeed, except for Zn, trace metal demands for lactation are negligible. Thus, when DM intake increases to support milk production, dietary trace metal intakes increase disproportionally to their requirements, resulting in a risk for unregulated absorption that may not be compensated by endogenous excretion. Therefore, considering dietary trace metal adequacy in terms of daily intake is better than only considering dietary concentrations. Defining lower and upper boundaries for dietary supply allows for a more adequate prevention of risk for deficiency or excess supply.
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Affiliation(s)
- J B Daniel
- Trouw Nutrition R&D, Amersfoort, the Netherlands.
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Osadchyi V, Van Antwerp SN, Vredenburgh J. Zinc-Induced Copper Deficiency Myeloneuropathy Masquerading as Paraneoplastic Syndrome: A Case Report. Cureus 2025; 17:e82995. [PMID: 40416147 PMCID: PMC12103893 DOI: 10.7759/cureus.82995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2025] [Indexed: 05/27/2025] Open
Abstract
Copper deficiency is a rare but reversible cause of myeloneuropathy, often overlooked in patients presenting with progressive neurological deficits. Excessive zinc intake, particularly from denture adhesives, can lead to copper depletion through competitive inhibition of intestinal absorption. We present the case of a 63-year-old female with a history of chronic obstructive pulmonary disease (COPD), Stage IIIA triple-negative breast cancer (TNBC) (status post mastectomy with adjuvant therapy), peripheral neuropathy, and a prior cecal adenoma who was admitted for hematochezia and progressive generalized weakness over several weeks. Imaging revealed a suspicious 1.4 cm pulmonary nodule in the left lower lobe and a 2.6 cm x 1.8 cm x 1.5 cm destructive lytic lesion in the left parietal bone. Given her worsening lower extremity weakness, concern for a paraneoplastic syndrome prompted a lumbar puncture and paraneoplastic antibody panel, both of which were negative. The patient underwent a five-day course of intravenous immunoglobulin (IVIG) without improvement. Further metabolic workup revealed profound copper deficiency of 417 µg/L (reference range: 810-1,990 µg/L). Upon further questioning, the patient reported chronic use of zinc-containing denture adhesive. She was initiated on copper supplementation with significant neurological improvement over several months, transitioning from being wheelchair bound to ambulating with a walker. Pathology from resection of the skull lesion revealed a World Health Organization (WHO) grade 1 meningioma, while the lung lesion was treated with CyberKnife, confirming Stage IA squamous cell carcinoma. This case highlights the importance of considering nutritional deficiencies in patients with symptoms of progressive myeloneuropathy, such as gait disturbances, sensory ataxia, or spasticity, particularly in those with risk factors such as chronic denture adhesive use. Clinicians should maintain a high index of suspicion for copper deficiency in cases mimicking paraneoplastic syndromes.
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Affiliation(s)
| | | | - James Vredenburgh
- Hematology and Oncology, Saint Francis Hospital and Medical Center, Hartford, USA
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Złowocka-Perłowska E, Baszuk P, Marciniak W, Derkacz R, Tołoczko-Grabarek A, Gołębiewska K, Słojewski M, Gołąb A, Lemiński A, Soczawa M, Scott RJ, Lubiński J. Blood and Serum Copper and Zinc Levels and 10-Year Survival of Patients After Kidney Cancer Diagnosis. Nutrients 2025; 17:944. [PMID: 40289930 PMCID: PMC11944747 DOI: 10.3390/nu17060944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Copper (Cu) and zinc (Zn) are essential trace elements, and an imbalance in their levels may influence the progression of cancer. The role of Cu and Zn levels in blood and serum, as well as 10-year survival rates in kidney cancer patients, remains unclear. Our objective was to determine the association between these micronutrients and mortality of kidney cancer patients. In this prospective study, we examined 284 consecutive, unselected kidney cancer patients and assessed their 10-year survival in relation to Cu and Zn levels. Methods: Micronutrient levels were measured using an inductively coupled plasma mass spectrometer. Each patient was categorized into one of four groups based on the distribution of Cu and Zn levels, ranked in increasing order. The multivariable models included factors such as age at diagnosis, gender, smoking history, type of surgery, and histopathological results. Results: We observed a significantly higher risk of all-cause mortality in patients with the highest blood or serum copper levels compared to those with the lower levels (blood: HR = 4.89; p < 0.001; serum: HR = 3.75; p < 0.001). With regard to zinc, we found a trend where lower blood or serum zinc levels (I quartile) were associated with higher mortality. Additionally, we identified a significant correlation between the Zn/Cu ratio and mortality. Conclusions: Patients in the lowest Zn/Cu ratio quartile had elevated hazard ratios compared to those in the higher quartile with HRs of 3.05 (p < 0.002) in blood and 5.72 (p < 0.001) in serum. To our knowledge, this study is the first to investigate the relationship between blood and serum levels of copper and zinc and kidney cancer survival.
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Affiliation(s)
- Elżbieta Złowocka-Perłowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, 70-204 Szczecin, Poland; (P.B.); (A.T.-G.); (K.G.); (J.L.)
| | - Piotr Baszuk
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, 70-204 Szczecin, Poland; (P.B.); (A.T.-G.); (K.G.); (J.L.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Wojciech Marciniak
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Róża Derkacz
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Aleksandra Tołoczko-Grabarek
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, 70-204 Szczecin, Poland; (P.B.); (A.T.-G.); (K.G.); (J.L.)
| | - Katarzyna Gołębiewska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, 70-204 Szczecin, Poland; (P.B.); (A.T.-G.); (K.G.); (J.L.)
| | - Marcin Słojewski
- Department of Urology and Oncological Urology Clinic, Pomeranian Medical University, 70-204 Szczecin, Poland; (M.S.); (A.G.); (M.S.)
| | - Adam Gołąb
- Department of Urology and Oncological Urology Clinic, Pomeranian Medical University, 70-204 Szczecin, Poland; (M.S.); (A.G.); (M.S.)
| | - Artur Lemiński
- Department of Biochemical Research, Pomeranian Medical University, 70-204 Szczecin, Poland;
| | - Michał Soczawa
- Department of Urology and Oncological Urology Clinic, Pomeranian Medical University, 70-204 Szczecin, Poland; (M.S.); (A.G.); (M.S.)
| | - Rodney J. Scott
- School of Biomedical Sciences and Pharmacy, Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW 2305, Australia;
- Division of Molecular Medicine, Pathology North, NSW Pathology, Newcastle, NSW 2305, Australia
| | - Jan Lubiński
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, 70-204 Szczecin, Poland; (P.B.); (A.T.-G.); (K.G.); (J.L.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
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Makiabadi E, Nasrollahzadeh J, Nakhaeizadeh R, Shahparvari MR, Roohelhami E. Effects of Perioperative Zinc Supplementation on Copper Circulating Levels and Expression of Metallothionein and Copper Antioxidant Chaperone-1 in Leukocytes in Patients Undergoing CABG Surgery. Biol Trace Elem Res 2025; 203:1297-1304. [PMID: 38865064 DOI: 10.1007/s12011-024-04259-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 06/01/2024] [Indexed: 06/13/2024]
Abstract
The use of zinc supplement may have a negative effect on copper status. The objective of this study was to evaluate the effect of zinc and vitamin E supplementation on copper and zinc biomarkers in patients undergoing coronary artery bypass graft (CABG) surgery. The study was an add-on project to a previously published randomized controlled trial (NCT05402826) on patients undergoing CABG surgery. Patients in the zinc-vitamin E group (n = 40) received oral zinc (120 mg) and vitamin E (1200 international units) 1 day before surgery, followed by 30 mg of zinc and 200 units of vitamin E per day until 21 days after surgery, while those in the control group (n = 38) received placebo. Plasma levels of copper, ceruloplasmin, superoxide dismutase (SOD) activity, as well as leukocyte gene expression of metallothionein 2A (MT2A) and antioxidant protein 1 (ATOX1), were determined 3 and 21 days after surgery. The plasma copper level in the zinc-vitamin E group was significantly lower than the placebo group on the 3rd postoperative day, but no significant between-group differences were observed on day 21. Plasma ceruloplasmin concentration and SOD activity were not different. Relative mRNA expression of leukocyte MT2A was increased at both times (days 3 and 21 in the zinc-vitamin E group compared to placebo, but ATOX1 expression was not affected. Although the plasma copper level was transiently decreased early after surgery in the zinc-vitamin E group, considering the lack of change in other copper biomarkers, it seems that the use of zinc supplements at the dose used in the present study does not have a significant negative effect on the role of intracellular copper.
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Affiliation(s)
- Elham Makiabadi
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Nasrollahzadeh
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Reza Nakhaeizadeh
- Department of Surgery, School of Medicine, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Reza Shahparvari
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elham Roohelhami
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Peng T, Liu C, Qian Y. Copper homeostasis and pregnancy complications: a comprehensive review. J Assist Reprod Genet 2025; 42:707-720. [PMID: 39792348 PMCID: PMC11950587 DOI: 10.1007/s10815-024-03375-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 12/18/2024] [Indexed: 01/12/2025] Open
Abstract
Pregnancy complications pose challenges for both pregnant women and obstetricians globally, with the pathogenesis of many remaining poorly understood. Recently coined as a mode of cell death, cuproptosis has been proposed but remains largely unexplored. This process involves copper overload, resulting in the accumulation of fatty acylated proteins and subsequent loss of iron-sulfur cluster proteins. This cascade induces proteotoxic stress, leading to cell death. In recent years, studies have indicated a connection between abnormal copper metabolism and several pregnancy-related diseases, including maternal placental dysplasia, gestational diabetes mellitus (GDM), gestational hypertension (PIH), preterm birth or abortion, as well as conditions in offspring such as intrauterine growth restriction (IUGR), allergic disease, Menkes disease, and Wilson's disease. Investigating the mechanism of cuproptosis and abnormal copper metabolism in these pregnancy-related diseases emerges as a critical research area. This article provides a concise review of cuproptosis mechanisms and emphasizes the association between abnormal copper metabolism and pregnancy-related diseases. Nevertheless, the doubtful viewpoints were also discussed.
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Affiliation(s)
- Tongyu Peng
- The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Chenglin Liu
- Chongqing Medical University, Chongqing, 400016, China
| | - Yuanmin Qian
- Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
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Galiot L, Audet I, Ouattara B, Bissonnette N, Talbot G, Raymond F, Deschênes T, Lessard M, Lapointe J, Guay F, Matte JJ. Effect of Neonatal Interventions with Specific Micronutrients and Bovine Colostrum on Micronutrient and Oxidative Statuses and on Gut Microbiota in Piglets from Birth to Post-Weaning Period. Vet Sci 2025; 12:151. [PMID: 40005911 PMCID: PMC11860533 DOI: 10.3390/vetsci12020151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/04/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
This study aimed to determine the impact of supplementations of copper, vitamins A and D (ADCU), and a bovine colostrum extract (BC) on the micronutrient status, antioxidant status, and intestinal microbiota of piglets until the post-weaning period. Twenty-three sows were fed conventional gestation and lactation diets, and twenty-four sows were fed conventional diets supplemented with ADCU. For each litter, all piglets received one of four treatments during lactation: no supplementation; ADCU; BC; and ADCU + BC. Within each litter, one low (LW) and one high birth weight (HW) piglet were euthanized before and after weaning to collect liver and intestinal samples. Serum vitamin D, liver retinol, and liver Cu were greater in ADCU piglets (p < 0.01), mostly before weaning. After weaning, liver Cu decreased markedly with a drop of 75% in all treatments, despite high levels of Cu in their post-weaning diets. The antioxidant status of piglets was not globally altered by treatments (p > 0.05). For microbiota composition, sow supplementation increased (p < 0.01) richness in bacterial species in the piglet colon, either before or shortly after weaning. Short-chain fatty acids in caecal digesta were increased by sow supplementation in LW piglets before weaning at 16 days of age (p < 0.05). In conclusion, oral supplementations to piglets increased postnatal micronutrient statuses during lactation, but this did not generally persist after weaning. Treatments to sows or piglets did not improve the response of piglets to oxidative stress, but supplementation to sows favoured gut microbiota diversity, particularly in LW piglets.
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Affiliation(s)
- Lucie Galiot
- Département des Sciences Animales, Université Laval, Ville de Québec, QC G1V 0A6, Canada; (L.G.); (F.G.)
| | - Isabelle Audet
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
| | - Bazoumana Ouattara
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
- Biological Sciences, Animal Biology, Université Peleforo GON COULIBALY, Korhogo 1328, Côte d’Ivoire
| | - Nathalie Bissonnette
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
| | - Guylaine Talbot
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
| | - Frédéric Raymond
- École de Nutrition, Centre Nutrition, Santé et Société (NUTRISS), et Institut de la Nutrition et des Aliments Fonctionnels (INAF), Université Laval, Ville de Québec, QC G1V 0A6, Canada; (F.R.); (T.D.)
| | - Thomas Deschênes
- École de Nutrition, Centre Nutrition, Santé et Société (NUTRISS), et Institut de la Nutrition et des Aliments Fonctionnels (INAF), Université Laval, Ville de Québec, QC G1V 0A6, Canada; (F.R.); (T.D.)
| | - Martin Lessard
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
| | - Jérôme Lapointe
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
| | - Frédéric Guay
- Département des Sciences Animales, Université Laval, Ville de Québec, QC G1V 0A6, Canada; (L.G.); (F.G.)
| | - Jean Jacques Matte
- Agriculture et Agroalimentaire Canada, Centre de Recherche et de Développement de Sherbrooke, Sherbrooke, QC J1M 0C8, Canada; (I.A.); (B.O.); (N.B.); (G.T.); (M.L.); (J.L.)
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Shi Y, Hao R, Ji H, Gao L, Yang J. Dietary zinc supplements: beneficial health effects and application in food, medicine and animals. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:5660-5674. [PMID: 38415843 DOI: 10.1002/jsfa.13325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 01/22/2024] [Indexed: 02/29/2024]
Abstract
Zinc, a crucial trace element is vital for the growth and development of humans. It is frequently described as 'the flower of life' and 'the source of intelligence'. Zinc supplements play a pivotal role in addressing zinc deficiency by serving as a vital source of this essential micronutrients, effectively replenishing depleted zinc levels in the body. In this paper, we first described the biological behavior of zinc in the human body and briefly described the physiological phenomena associated with zinc levels. The benefits and drawbacks of various zinc supplement forms are then discussed, with emphasis on the most recent zinc supplement formulations. Finally, the application of zinc supplements in food, medicine, and animal husbandry is further summarized. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Ying Shi
- School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, China
| | - Rui Hao
- School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, China
| | - Haixia Ji
- School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, China
| | - Li Gao
- School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, China
| | - Junyan Yang
- School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi, China
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9
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Li L, Zhou H, Zhang C. Cuproptosis in cancer: biological implications and therapeutic opportunities. Cell Mol Biol Lett 2024; 29:91. [PMID: 38918694 PMCID: PMC11201306 DOI: 10.1186/s11658-024-00608-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 06/12/2024] [Indexed: 06/27/2024] Open
Abstract
Cuproptosis, a newly identified copper (Cu)-dependent form of cell death, stands out due to its distinct mechanism that sets it apart from other known cell death pathways. The molecular underpinnings of cuproptosis involve the binding of Cu to lipoylated enzymes in the tricarboxylic acid cycle. This interaction triggers enzyme aggregation and proteotoxic stress, culminating in cell death. The specific mechanism of cuproptosis has yet to be fully elucidated. This newly recognized form of cell death has sparked numerous investigations into its role in tumorigenesis and cancer therapy. In this review, we summarized the current knowledge on Cu metabolism and its link to cancer. Furthermore, we delineated the molecular mechanisms of cuproptosis and summarized the roles of cuproptosis-related genes in cancer. Finally, we offered a comprehensive discussion of the most recent advancements in Cu ionophores and nanoparticle delivery systems that utilize cuproptosis as a cutting-edge strategy for cancer treatment.
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Affiliation(s)
- Liping Li
- Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People's Republic of China
| | - Houfeng Zhou
- Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People's Republic of China
| | - Chenliang Zhang
- Division of Abdominal Cancer, Department of Medical Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
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10
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Bourgon N, Tacail T, Jaouen K, Leichliter JN, McCormack J, Winkler DE, Clauss M, Tütken T. Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach. Metallomics 2024; 16:mfae026. [PMID: 38755021 PMCID: PMC11157155 DOI: 10.1093/mtomcs/mfae026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/15/2024] [Indexed: 05/18/2024]
Abstract
The stable isotope composition of zinc (δ66Zn), which is an essential trace metal for many biological processes in vertebrates, is increasingly used in ecological, archeological, and paleontological studies to assess diet and trophic level discrimination among vertebrates. However, the limited understanding of dietary controls and isotopic fractionation processes on Zn isotope variability in animal tissues and biofluids limits precise dietary reconstructions. The current study systematically investigates the dietary effects on Zn isotope composition in consumers using a combined controlled feeding experiment and box-modeling approach. For this purpose, 21 rats were fed one of seven distinct animal- and plant-based diets and a total of 148 samples including soft and hard tissue, biofluid, and excreta samples of these individuals were measured for δ66Zn. Relatively constant Zn isotope fractionation is observed across the different dietary groups for each tissue type, implying that diet is the main factor controlling consumer tissue δ66Zn values, independent of diet composition. Furthermore, a systematic δ66Zn diet-enamel fractionation is reported for the first time, enabling diet reconstruction based on δ66Zn values from tooth enamel. In addition, we investigated the dynamics of Zn isotope variability in the body using a box-modeling approach, providing a model of Zn isotope homeostasis and inferring residence times, while also further supporting the hypothesis that δ66Zn values of vertebrate tissues are primarily determined by that of the diet. Altogether this provides a solid foundation for refined (paleo)dietary reconstruction using Zn isotopes of vertebrate tissues.
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Affiliation(s)
- Nicolas Bourgon
- IsoTROPIC research group, Max Planck Institute for Geoanthropology, Kahlaische Str. 10, Jena, Germany
- Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, Germany
- Institute of Geosciences, Johannes Gutenberg University, Johann-Joachim-Becher-Weg 21, Mainz, Germany
| | - Théo Tacail
- Institute of Geosciences, Johannes Gutenberg University, Johann-Joachim-Becher-Weg 21, Mainz, Germany
| | - Klervia Jaouen
- Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, Germany
- Géosciences Environnement Toulouse, Observatoire Midi Pyrénées, 14 avenue Edouard Belin, Toulouse, France
| | - Jennifer N Leichliter
- Institute of Geosciences, Johannes Gutenberg University, Johann-Joachim-Becher-Weg 21, Mainz, Germany
- HoMeCo Emmy Noether research group, Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, Mainz, Germany
| | - Jeremy McCormack
- Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, Germany
- Department of Geosciences, Goethe University Frankfurt, Altenhöferallee 1, Frankfurt, Germany
| | - Daniela E Winkler
- Institute of Geosciences, Johannes Gutenberg University, Johann-Joachim-Becher-Weg 21, Mainz, Germany
- Zoology and Functional Morphology of Vertebrates, Zoological Institute, University Kiel, Am Botanischen Garten 3–9, Kiel, Germany
| | - Marcus Clauss
- Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, Winterthurerstr. 260, Zurich, Switzerland
| | - Thomas Tütken
- Institute of Geosciences, Johannes Gutenberg University, Johann-Joachim-Becher-Weg 21, Mainz, Germany
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11
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Matuszczak M, Kiljańczyk A, Marciniak W, Derkacz R, Stempa K, Baszuk P, Bryśkiewicz M, Sun P, Cheriyan A, Cybulski C, Dębniak T, Gronwald J, Huzarski T, Lener MR, Jakubowska A, Szwiec M, Stawicka-Niełacna M, Godlewski D, Prusaczyk A, Jasiewicz A, Kluz T, Tomiczek-Szwiec J, Kilar-Kobierzycka E, Siołek M, Wiśniowski R, Posmyk R, Jarkiewicz-Tretyn J, Scott RJ, Narod SA, Lubiński J. Zinc and Its Antioxidant Properties: The Potential Use of Blood Zinc Levels as a Marker of Cancer Risk in BRCA1 Mutation Carriers. Antioxidants (Basel) 2024; 13:609. [PMID: 38790714 PMCID: PMC11118047 DOI: 10.3390/antiox13050609] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 05/08/2024] [Accepted: 05/14/2024] [Indexed: 05/26/2024] Open
Abstract
BRCA1 mutations predispose women to breast and ovarian cancer. The anticancer effect of zinc is typically linked to its antioxidant abilities and protecting cells against oxidative stress. Zinc regulates key processes in cancer development, including DNA repair, gene expression, and apoptosis. We took a blood sample from 989 female BRCA1 mutation carriers who were initially unaffected by cancer and followed them for a mean of 7.5 years thereafter. There were 172 incident cases of cancer, including 121 cases of breast cancer, 29 cases of ovarian cancers, and 22 cancers at other sites. A zinc level in the lowest tertile was associated with a modestly higher risk of ovarian cancer compared to women with zinc levels in the upper two tertiles (HR = 1.65; 95% CI 0.80 to 3.44; p = 0.18), but this was not significant. Among those women with zinc levels in the lowest tertile, the 10-year cumulative risk of ovarian cancer was 6.1%. Among those in the top two tertiles of zinc level, the ten-year cumulative risk of ovarian cancer was 4.7%. There was no significant association between zinc level and breast cancer risk. Our preliminary study does not support an association between serum zinc level and cancer risk in BRCA1 mutation carriers.
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Affiliation(s)
- Milena Matuszczak
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Adam Kiljańczyk
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Wojciech Marciniak
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Róża Derkacz
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Klaudia Stempa
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Piotr Baszuk
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Marta Bryśkiewicz
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Ping Sun
- Women’s College Research Institute, Women’s College Hospital, University of Toronto, Toronto, ON M5G 1N8, Canada; (P.S.); (A.C.)
| | - Angela Cheriyan
- Women’s College Research Institute, Women’s College Hospital, University of Toronto, Toronto, ON M5G 1N8, Canada; (P.S.); (A.C.)
| | - Cezary Cybulski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Tadeusz Dębniak
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Jacek Gronwald
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
| | - Tomasz Huzarski
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
- Department of Clinical Genetics and Pathology, University of Zielona Góra, ul. Zyty 28, 65-046 Zielona Góra, Poland
| | - Marcin R. Lener
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Anna Jakubowska
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
| | - Marek Szwiec
- Department of Surgery and Oncology, University of Zielona Góra, Zyty 28, 65-046 Zielona Góra, Poland
| | - Małgorzata Stawicka-Niełacna
- Department of Clinical Genetics and Pathology, University of Zielona Góra, ul. Zyty 28, 65-046 Zielona Góra, Poland
| | | | | | - Andrzej Jasiewicz
- Genetic Counseling Center, Subcarpatian Oncological Hospital, 18 Bielawskiego St., 36-200 Brzozów, Poland;
| | - Tomasz Kluz
- Department of Gynecology, Gynecology Oncology and Obstetrics, Institute of Medical Sciences, Medical College, Rzeszow University, Rejtana 16c, 35-959 Rzeszow, Poland
| | - Joanna Tomiczek-Szwiec
- Department of Histology, Department of Biology and Genetics, Faculty of Medicine, University of Opole, 45-040 Opole, Poland;
| | - Ewa Kilar-Kobierzycka
- Department of Oncology, District Specialist Hospital, Leśna 27-29 St., 58-100 Świdnica, Poland;
| | - Monika Siołek
- Holycross Cancer Center, Artwińskiego 3 St., 25-734 Kielce, Poland;
| | - Rafał Wiśniowski
- Regional Oncology Hospital, Wyzwolenia 18 St., 43-300 Bielsko Biała, Poland;
| | - Renata Posmyk
- Department of Clinical Genetics, Medical University of Bialystok, 15-089 Białystok, Poland;
| | | | - Rodney J. Scott
- Medical Genetics, Hunter Medical Research Institute, Priority Research Centre for Cancer Research, Innovation and Translation, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Pathology North, John Hunter Hospital, King and Auckland Streets, Newcastle, NSW 2300, Australia;
| | - Steven A. Narod
- Women’s College Research Institute, Women’s College Hospital, University of Toronto, Toronto, ON M5G 1N8, Canada; (P.S.); (A.C.)
| | - Jan Lubiński
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252 Szczecin, Poland; (M.M.); (A.K.); (K.S.); (M.B.); (C.C.); (T.D.); (J.G.); (T.H.)
- Read-Gene, Grzepnica, ul. Alabastrowa 8, 72-003 Dobra, Poland; (W.M.); (R.D.)
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12
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Kirk FT, Munk DE, Swenson ES, Quicquaro AM, Vendelbo MH, Schilsky ML, Ott P, Sandahl TD. Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64 Cu PET/CT study in healthy humans. Hepatology 2024; 79:1065-1074. [PMID: 38088886 PMCID: PMC11019997 DOI: 10.1097/hep.0000000000000708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 11/17/2023] [Indexed: 02/24/2024]
Abstract
BACKGROUND AND AIMS Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption. APPROACH AND RESULTS Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 ( 64 Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64 Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64 Cu uptake reflect the effect of drugs on intestinal absorption. 64 Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64 Cu activity 1 hour after 64 Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p <0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p <0.02, indicating strong inhibition of intestinal 64 Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p <0.04. CONCLUSIONS In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.
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Affiliation(s)
- Frederik Teicher Kirk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Ditte Emilie Munk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | - Mikkel Holm Vendelbo
- Department of Nuclear Medicine & PET-center, Aarhus University Hospital, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Michael L. Schilsky
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Surgery, Section of Transplant and Immunology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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13
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Delle Cave V, Di Dato F, Iorio R. Wilson's Disease with Acute Hepatic Onset: How to Diagnose and Treat It. CHILDREN (BASEL, SWITZERLAND) 2024; 11:68. [PMID: 38255382 PMCID: PMC10814100 DOI: 10.3390/children11010068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/19/2023] [Accepted: 01/05/2024] [Indexed: 01/24/2024]
Abstract
Wilson's disease (WD) with acute onset poses a diagnostic challenge because it is clinically indistinguishable from other acute liver diseases. In addition, serum ceruloplasmin and urinary copper excretion, the first-line diagnostic tools for WD, can show false positive results in the case of acute liver failure, and the diagnostic role of genetic analysis is limited by the time required to perform it. In the case of fulminant onset, there is a clear indication of liver transplantation. "New Wilson Index" is frequently used to discriminate between patients who need liver transplantation versus those who can be successfully managed by medical treatment, but its reliability remains controversial. Timely referral of patients with acute liver failure due to WD may be a key factor in improving patient survival. Although liver transplant very often represents the only chance for such patients, maximum effort should be made to promote survival with a native liver. The management of these aspects of WD is still a matter of debate and will be the subject of this review.
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Affiliation(s)
| | | | - Raffaele Iorio
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (V.D.C.); (F.D.D.)
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14
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Welham S, Rose P, Kirk C, Coneyworth L, Avery A. Mineral Supplements in Ageing. Subcell Biochem 2024; 107:269-306. [PMID: 39693029 DOI: 10.1007/978-3-031-66768-8_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
With advancing age, achievement of dietary adequacy for all nutrients is increasingly difficult and this is particularly so for minerals. Various factors impede mineral acquisition and absorption including reduced appetite, depressed gastric acid production and dysregulation across a range of signalling pathways in the intestinal mucosa. Minerals are required in sufficient levels since they are critical for the proper functioning of metabolic processes in cells and tissues, including energy metabolism, DNA and protein synthesis, immune function, mobility, and skeletal integrity. When uptake is diminished or loss exceeds absorption, alternative approaches are required to enable individuals to maintain adequate mineral levels. Currently, supplementation has been used effectively in populations for the restoration of levels of some minerals like iron, zinc, and calcium, but these may not be without inherent challenges. Therefore, in this chapter we review the current understanding around the effectiveness of mineral supplementation for the minerals most clinically relevant for the elderly.
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Affiliation(s)
- Simon Welham
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK.
| | - Peter Rose
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK
| | - Charlotte Kirk
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK
| | - Lisa Coneyworth
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK
| | - Amanda Avery
- Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK
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15
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Galiot L, Audet I, Ouattara B, Lo Verso L, Bissonnette N, Guy B, Litta G, Talbot G, Lessard M, Lapointe J, Guay F, Matte JJ. Effects of sources and routes of administration of vitamins A, D and copper on postnatal status of these micronutrients in piglets. Transl Anim Sci 2023; 8:txad138. [PMID: 38304120 PMCID: PMC10833445 DOI: 10.1093/tas/txad138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 12/22/2023] [Indexed: 02/03/2024] Open
Abstract
Twenty-six nulliparous sows were fed conventional gestation and lactation diets supplemented (N = 13) or not (N = 13) with extra daily supplements of 25-hydroxy-cholecalciferol (25-OH-D3; 4 ĸIU), β-carotene (24 ĸIU), and copper (Cu)-proteinate (45 mg) from day 90 of gestation to 21 d of lactation (L21). In each litter, 10 piglets were divided into 5 pairs received, at 2 (L2) and 8 d (L8) of age, one of the five combinations of micronutrient sources and routes of administration (N = 260 piglets total). These neonatal treatments (N = 26 pairs or 52 piglets each) consisted of oral vitamin D3, retinol acetate and CuSO4 (T1); oral 25-OH-D3, β-carotene, and Cu proteinate (T2); exposure to ultraviolet light (UVB), oral retinol palmitate and Cu gluconate (T3); intramuscular vitamin D3 and retinyl propionate and oral Cu acetate (T4); oral saline (CTRL). Oral or intramuscular provisions corresponded to 12 mg of Cu and 70 and 12 ĸIU of vitamins A and D, respectively. Blood samples were collected from all piglets at L2, L8, and L21 for determination of serum Cu, retinol, and 25-OH-D3. Body weight was measured at birth, L2, L8, and L21. Piglets were weaned at L21, and liver and blood samples were collected 2 d later to evaluate oxidative enzymes in blood and liver and hepatic ATP concentrations and expression of genes associated with antioxidant status. Sow treatments had marginal or no impacts on Cu, retinol, 25-OH-D3, or antioxidant status in piglet blood serum and liver. However, when supplements were given to piglets, hepatic Cu was 38% greater in for all treated piglets compared to CTRL (P < 0.01), hepatic retinol was 3 times higher in T1 than in CTRL (P < 0.01) and intermediate for other treatments whereas serum 25-OH-D3 was markedly increased with T2 and T3 at L8 and L21, respectively, compared to CTRL (Piglet treatment × Age interaction, P < 0.01). Concerning antioxidant activities, glutathione peroxidase, and superoxide dismutase were increased (P < 0.03) in plasma of T2 piglets whereas the highest values (P < 0.03) for indicators of oxidative damage to proteins were observed in T4 piglets. The study revealed that oral Cu proteinate from T2, oral retinol acetate from T1, oral 25-hydroxy-cholecalciferol from T2, and UVB light exposure from T3 were the most efficient ways of increasing the postnatal status of these micronutrients in suckling piglets and this may have some impacts on their peri-weaning antioxidant status.
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Affiliation(s)
- Lucie Galiot
- Département des Sciences Animales, Université Laval, Québec, QC, G1V 0A6, Canada
| | - Isabelle Audet
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Bazoumana Ouattara
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Luca Lo Verso
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Nathalie Bissonnette
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Bertrand Guy
- DNP R&D Analytics, DSM Nutritional Products Ltd., Kaiseraugst, 4303, Switzerland
| | - Gilberto Litta
- DNP R&D Analytics, DSM Nutritional Products Ltd., Kaiseraugst, 4303, Switzerland
| | - Guylaine Talbot
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Martin Lessard
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Jérôme Lapointe
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
| | - Frédéric Guay
- Département des Sciences Animales, Université Laval, Québec, QC, G1V 0A6, Canada
| | - Jean Jacques Matte
- Agriculture and Agri-Food Canada, Centre de recherche et de développement de Sherbrooke, Sherbrooke, QC, J0B 1L0, Canada
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16
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Kim HJ, Jin XH, Kang SW, Kim YY. Effects of dietary trace mineral levels on physiological responses, reproductive performance, litter performance, blood profiles, and milk composition in gestating sows. Anim Biosci 2023; 36:1860-1868. [PMID: 37641834 PMCID: PMC10623021 DOI: 10.5713/ab.23.0193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/05/2023] [Accepted: 07/19/2023] [Indexed: 08/31/2023] Open
Abstract
OBJECTIVE This study was conducted to evaluate the effects of optimal trace mineral levels on the physiological responses, reproductive performance, litter performance, blood profiles and milk composition in gestating sows. METHODS A total of 59 multiparous sows (Yorkshire×Landrace) with similar body weight (BW), backfat thickness (BF), and parity were assigned to one of four treatments with 14 or 15 sows per treatment using a completely randomized design. The treatments were 100% (M1), 300% (M3), 600% (M6), and 900% (M9) of the National Research Council (NRC) Nutrient Requirements of Swine. During lactation period, all the sows were fed the same commercial lactation diet. RESULTS No significant differences were observed in the BW, BF, reproductive performance, milk composition, or growth performance of the piglets. On day 70 of gestation, the serum zinc concentration showed a quadratic response to M6 treatment (quadratic, p<0.05). Moreover, as the dietary mineral levels increased, the zinc concentration increased linearly at 110 days of gestation (linear, p<0.05). Furthermore, copper and iron concentrations in the serum of sows at 24 h postpartum decreased linearly when high levels of dietary minerals were provided (linear, p<0.05). In the serum of piglets, serum zinc concentrations decreased linearly (linear, p<0.05), and iron concentration showed a quadratic response (quadratic, p<0.05) with an increase in trace mineral premix levels in gestation diets. CONCLUSION The current trace mineral requirements of NRC (2012) are suitable for gestating sows, and the addition of dietary mineral levels in the gestating diet did not show any improvements during the gestation and lactation periods.
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Affiliation(s)
- Hong Jun Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826,
Korea
| | - Xing Hao Jin
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826,
Korea
| | - Sun Woo Kang
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826,
Korea
| | - Yoo Yong Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826,
Korea
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17
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Munk DE, Vendelbo MH, Kirk FT, Rewitz KS, Bender DA, Vase KH, Munk OL, Vilstrup H, Ott P, Sandahl TD. Distribution of non-ceruloplasmin-bound copper after i.v. 64Cu injection studied with PET/CT in patients with Wilson disease. JHEP Rep 2023; 5:100916. [PMID: 37886434 PMCID: PMC10597763 DOI: 10.1016/j.jhepr.2023.100916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/31/2023] [Accepted: 08/31/2023] [Indexed: 10/28/2023] Open
Abstract
Background & Aims In Wilson disease (WD), copper accumulation and increased non-ceruloplasmin-bound copper in plasma lead to liver and brain pathology. To better understand the fate of non-ceruloplasmin-bound copper, we used PET/CT to examine the whole-body distribution of intravenously injected 64-copper (64Cu). Methods Eight patients with WD, five heterozygotes, and nine healthy controls were examined by dynamic PET/CT for 90 min and static PET/CT up to 20 h after injection. We measured 64Cu activity in blood and tissue and quantified the kinetics by compartmental analysis. Results Initially, a large fraction of injected 64Cu was distributed to extrahepatic tissues, especially skeletal muscle. Thus, across groups, extrahepatic tissues accounted for 45-58% of the injected dose (%ID) after 10 min, and 45-55% after 1 h. Kinetic analysis showed rapid exchange of 64Cu between blood and muscle as well as adipose tissue, with 64Cu retention in a secondary compartment, possibly mitochondria. This way, muscle and adipose tissue may protect the brain from spikes in non-ceruloplasmin-bound copper. Tiny amounts of cerebral 64Cu were detected (0.2%ID after 90 min and 0.3%ID after 6 h), suggesting tight control of cerebral copper in accordance with a cerebral clearance that is 2-3-fold lower than in muscle. Compared to controls, patients with WD accumulated more hepatic copper 6-20 h after injection, and also renal copper at 6 h. Conclusion Non-ceruloplasmin-bound copper is initially distributed into a number of tissues before being redistributed slowly to the eliminating organ, the liver. Cerebral uptake of copper is extremely slow and likely highly regulated. Our findings provide new insights into the mechanisms of copper control. Impact and implications Maintaining non-ceruloplasmin-bound copper within the normal range is an important treatment goal in WD as this "free" copper is considered toxic to the liver and brain. We found that intravenously injected non-ceruloplasmin-bound copper quickly distributed to a number of tissues, especially skeletal muscle, subcutaneous fat, and the liver, while uptake into the brain was slow. This study offers new insights into the mechanisms of copper control, which may encourage further research into potential new treatment targets. Clinical trial number 2016-001975-59.
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Affiliation(s)
- Ditte Emilie Munk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Mikkel Holm Vendelbo
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Frederik Teicher Kirk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Karina Stubkjær Rewitz
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Dirk Andreas Bender
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Karina Højrup Vase
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Ole Lajord Munk
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Huang L, Wang Z, Liu J, Wan M, Liu J, Liu F, Tu X, Xiao J, Liao X, Lu H, Zhang S, Cao Z. Apatinib induces zebrafish hepatotoxicity by inhibiting Wnt signaling and accumulation of oxidative stress. ENVIRONMENTAL TOXICOLOGY 2023; 38:2679-2690. [PMID: 37551640 DOI: 10.1002/tox.23902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 05/17/2023] [Accepted: 07/06/2023] [Indexed: 08/09/2023]
Abstract
Apatinib, a small-molecule VEGFR2-tyrosine kinase inhibitor, has shown potent anticancer activity in various clinical cancer treatments, but also different adverse reactions. Therefore, it is necessary to study its potential toxicity and working mechanism. We used zebrafish to investigate the effects of apatinib on the development of embryos. Zebrafish exposed to 2.5, 5, and 10 μM apatinib showed adverse effects such as decreased liver area, pericardial oedema, slow yolk absorption, bladder atrophy, and body length shortening. At the same time, it leads to abnormal liver tissue structure, liver function and related gene expression. Furthermore, after exposure to apatinib, oxidative stress levels were significantly elevated but liver developmental toxicity was effectively ameliorated with oxidative stress inhibitor treatment. Apatinib induces down-regulation of key target genes of Wnt signaling pathway in zebrafish, and it is found that Wnt activator can significantly rescue liver developmental defects. These results suggest that apatinib may induce zebrafish hepatotoxicity by inhibiting the Wnt signaling pathway and up-regulating oxidative stress, helping to strengthen our understanding of rational clinical application of apatinib.
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Affiliation(s)
- Ling Huang
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Zhipeng Wang
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Jieping Liu
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Mengqi Wan
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Jiejun Liu
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Fasheng Liu
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Xiaofei Tu
- Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
| | - Juhua Xiao
- Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, China
| | - Xinjun Liao
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Huiqiang Lu
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
| | - Shouhua Zhang
- Department of General Surgery, The Affiliated Children's Hospital of Nanchang University, Nanchang, China
| | - Zigang Cao
- Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, China
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19
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Övermöhle C, Rimbach G, Waniek S, Strathmann EA, Liedtke T, Stürmer P, Both M, Weber KS, Lieb W. Association of Plasma Zinc and Copper with Body Composition, Lipids and Inflammation in a Cross-Sectional General Population Sample from Germany. Nutrients 2023; 15:4460. [PMID: 37892535 PMCID: PMC10609917 DOI: 10.3390/nu15204460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/15/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
We aimed to relate circulating plasma zinc and copper to a broad spectrum of adiposity-related traits in a cross-sectional Northern German study (n = 841, 42% female, age: 61 ± 12 years). Zinc and copper were measured by inductively coupled plasma-mass spectrometry. Subcutaneous (SAT) and visceral (VAT) adipose tissue and liver fat were derived from 534 and 538 participants, respectively, via magnet resonance imaging. Associations were assessed using multivariable-adjusted linear regression analysis. An increase per one standard deviation (SD) in zinc was associated with direct linear increases in body mass index (BMI) (1.17%; 95% confidence interval (95%CI) 0.15-2.20%), waist circumference (0.85%; 95%CI 0.04-1.67%) and waist-to-hip ratio (0.64%; 95%CI 0.18-1.09%). A 1-SD increment in copper was directly associated with BMI (1.64%; 0.41-2.88%) and waist circumference (1.22%; 95%CI 0.25-2.20%) but not waist-to-hip ratio. Independent of fat intake, zinc displayed associations with VAT (5.73%; 95%CI 2.04-9.56%) and with liver fat (3.84%; 95%CI 1.49-6.25%), the latter association being also independent of BMI. Copper was directly associated with SAT (4.64%; 95%CI 0.31-9.15%) before accounting for BMI, but showed no association with VAT or liver fat. Observed associations suggest a possible relevance of zinc and copper to adiposity. Particularly zinc displayed associations with traits of abdominal adiposity and liver fat.
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Affiliation(s)
- Cara Övermöhle
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, Kiel University, 24118 Kiel, Germany
| | - Sabina Waniek
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Eike A. Strathmann
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Tatjana Liedtke
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Paula Stürmer
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Marcus Both
- Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
| | - Katharina S. Weber
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
| | - Wolfgang Lieb
- Institute of Epidemiology, Kiel University, 24105 Kiel, Germany (K.S.W.); (W.L.)
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20
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Zhou B, Li J, Zhang J, Liu H, Chen S, He Y, Wang T, Wang C. Effects of Long-Term Dietary Zinc Oxide Nanoparticle on Liver Function, Deposition, and Absorption of Trace Minerals in Intrauterine Growth Retardation Pigs. Biol Trace Elem Res 2023; 201:4746-4757. [PMID: 36585599 DOI: 10.1007/s12011-022-03547-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/24/2022] [Indexed: 12/31/2022]
Abstract
To investigate the long-term effects of dietary zinc oxide nanoparticle (Nano-ZnO, 20-40 nm) on the relative organ weight, liver function, deposition, and absorption of trace minerals in intrauterine growth retardation (IUGR) pigs, piglets were allocated to NBW (6 normal birth weight piglets fed basal diets), IUGR (6 IUGR piglets fed basal diets) and IUGR+NZ (6 IUGR piglets fed basal diets + 600 mg Zn/kg from Nano-ZnO) groups at weaning (21 days of age), which were sampled at 163 days of age. There were no noteworthy changes in the relative weight of organs, hepatic histomorphology, serum alkaline phosphatase, glutamic pyruvic transaminase and glutamic oxalacetic transaminase activities, and Mn, Cu, and Fe concentrations in leg muscle, the liver, the tibia, and feces among the IUGR, NBW, and IUGR+NZ groups (P>0.05), and no intact Nano-ZnO in the jejunum, liver, and muscle was observed, while dietary Nano-ZnO increased the Zn concentrations in the tibia, the liver, serum, and feces (P<0.05) and mRNA expression of metallothionein (MT) 1A, MT2A, solute carrier family 39 member (ZIP) 4, ZIP14, ZIP8, divalent metal transporter 1, solute carrier family 30 member (ZnT) 1, ZnT4 and metal regulatory transcription factor 1, and ZIP8 protein expression in jejunal mucosa (P<0.05). Immunohistochemistry showed that dietary Nano-ZnO increased the relative optical density of ZIP8 (mainly expressed in cells of brush border) and MT2A (mainly expressed in villus lamina propria and gland/crypt) (P<0.05). In conclusion, long-term dietary Nano-ZnO showed no obvious side effects on the development of the major organs, liver function, and metabolism of Cu, Fe, and Mn in IUGR pigs, while it increased the Zn absorption and deposition via enhancing the expression of transporters (MT, ZIP, and ZnT families) in the jejunum, rather than via endocytosis as the form of intact nanoparticles.
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Affiliation(s)
- Binbin Zhou
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Jian Li
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Jiaqi Zhang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Huijuan Liu
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Shun Chen
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Yudan He
- Department of Animal Science, Jiangxi Biotech Vocational College, 608 Nanlian Road, Nanchang, 330200, Jiangxi, People's Republic of China
| | - Tian Wang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China
| | - Chao Wang
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China.
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21
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Martinez-Morata I, Sobel M, Tellez-Plaza M, Navas-Acien A, Howe CG, Sanchez TR. A State-of-the-Science Review on Metal Biomarkers. Curr Environ Health Rep 2023; 10:215-249. [PMID: 37337116 PMCID: PMC10822714 DOI: 10.1007/s40572-023-00402-x] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 06/21/2023]
Abstract
PURPOSE OF REVIEW Biomarkers are commonly used in epidemiological studies to assess metals and metalloid exposure and estimate internal dose, as they integrate multiple sources and routes of exposure. Researchers are increasingly using multi-metal panels and innovative statistical methods to understand how exposure to real-world metal mixtures affects human health. Metals have both common and unique sources and routes of exposure, as well as biotransformation and elimination pathways. The development of multi-element analytical technology allows researchers to examine a broad spectrum of metals in their studies; however, their interpretation is complex as they can reflect different windows of exposure and several biomarkers have critical limitations. This review elaborates on more than 500 scientific publications to discuss major sources of exposure, biotransformation and elimination, and biomarkers of exposure and internal dose for 12 metals/metalloids, including 8 non-essential elements (arsenic, barium, cadmium, lead, mercury, nickel, tin, uranium) and 4 essential elements (manganese, molybdenum, selenium, and zinc) commonly used in multi-element analyses. RECENT FINDINGS We conclude that not all metal biomarkers are adequate measures of exposure and that understanding the metabolic biotransformation and elimination of metals is key to metal biomarker interpretation. For example, whole blood is a good biomarker of exposure to arsenic, cadmium, lead, mercury, and tin, but it is not a good indicator for barium, nickel, and uranium. For some essential metals, the interpretation of whole blood biomarkers is unclear. Urine is the most commonly used biomarker of exposure across metals but it should not be used to assess lead exposure. Essential metals such as zinc and manganese are tightly regulated by homeostatic processes; thus, elevated levels in urine may reflect body loss and metabolic processes rather than excess exposure. Total urinary arsenic may reflect exposure to both organic and inorganic arsenic, thus, arsenic speciation and adjustment for arsebonetaine are needed in populations with dietary seafood consumption. Hair and nails primarily reflect exposure to organic mercury, except in populations exposed to high levels of inorganic mercury such as in occupational and environmental settings. When selecting biomarkers, it is also critical to consider the exposure window of interest. Most populations are chronically exposed to metals in the low-to-moderate range, yet many biomarkers reflect recent exposures. Toenails are emerging biomarkers in this regard. They are reliable biomarkers of long-term exposure for arsenic, mercury, manganese, and selenium. However, more research is needed to understand the role of nails as a biomarker of exposure to other metals. Similarly, teeth are increasingly used to assess lifelong exposures to several essential and non-essential metals such as lead, including during the prenatal window. As metals epidemiology moves towards embracing a multi-metal/mixtures approach and expanding metal panels to include less commonly studied metals, it is important for researchers to have a strong knowledge base about the metal biomarkers included in their research. This review aims to aid metals researchers in their analysis planning, facilitate sound analytical decision-making, as well as appropriate understanding and interpretation of results.
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Affiliation(s)
- Irene Martinez-Morata
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, 1107, New York, NY, 10032, USA.
| | - Marisa Sobel
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, 1107, New York, NY, 10032, USA
| | - Maria Tellez-Plaza
- Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Ana Navas-Acien
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, 1107, New York, NY, 10032, USA
| | - Caitlin G Howe
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
| | - Tiffany R Sanchez
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, 1107, New York, NY, 10032, USA
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22
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Stephenson EL, Rathert-Williams AR, Kenny AL, Nagy DW, Shoemake BM, McFadden TB, Tucker HA, Meyer AM. Effects of copper, zinc, and manganese source and inclusion during late gestation on beef cow-calf performance, mineral transfer, and metabolism. Transl Anim Sci 2023; 7:txad097. [PMID: 37767050 PMCID: PMC10519816 DOI: 10.1093/tas/txad097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 08/11/2023] [Indexed: 09/29/2023] Open
Abstract
To determine effects of Cu, Zn, and Mn source and inclusion during late gestation, multiparous beef cows [n = 48; 649 ± 80 kg body weight (BW); 5.3 ± 0.5 body condition score (BCS)] were individually-fed hay and supplement to meet or exceed all nutrient recommendations except Cu, Zn, and Mn. From 91.2 ± 6.2 d pre-calving to 11.0 ± 3.2 d post-calving, cows received: no additional Cu, Zn, or Mn (control, CON), sulfate-based Cu, Zn, and Mn (inorganic, ITM) or metal methionine hydroxy analogue chelates (MMHAC) of Cu, Zn, and Mn at 133% recommendations, or a combination of inorganic and chelated Cu, Zn, and Mn (reduce and replace, RR) to meet 100% of recommendations. Data were analyzed with treatment and breeding group (and calf sex if P < 0.25 for offspring measures) as fixed effects, animal as experimental unit, and sampling time as a repeated effect for serum, plasma, and milk measures over time. Post-calving cow liver Cu was greater (P ≤ 0.07) in MMHAC compared with all other treatments. Calves born to RR had greater (P ≤ 0.05) liver Cu than ITM and CON, and MMHAC had greater (P = 0.06) liver Cu than CON. Liver Mn was less (P ≤ 0.08) for RR calves than all other treatments. Calf plasma Zn was maintained (P ≥ 0.15) from 0 to 48 h of age in ITM and MMHAC but decreased (P ≤ 0.03) in CON and RR. Gestational cow BW, BCS, and metabolites were not affected (P ≥ 0.13) by treatment, but gestational serum thiobarbituric acid reactive substances (TBARS) were greater (P = 0.01) for CON than MMHAC. Treatment did not affect (P ≥ 0.13) calf birth size, vigor, placental size and minerals, or transfer of passive immunity. Neonatal calf serum Ca was greater (P ≤ 0.05) for MMHAC than all other treatments; other calf serum chemistry and plasma cortisol were not affected (P ≥ 0.12). Pre-suckling colostrum yield, and lactose concentration and content, were greater (P ≤ 0.06) for MMHAC compared with ITM and RR. Colostral triglyceride and protein concentrations were greater (P ≤ 0.08) for RR than MMHAC and CON. Cow lactational BW and BCS, milk yield and composition, and pre-weaning calf BW and metabolism were not affected (P ≥ 0.13) by treatment. Lactational serum TBARS were greater (P = 0.04) for RR than CON at day 35 and greater (P ≤ 0.09) for MMHAC at day 60 than all other treatments. Source and inclusion of Cu, Zn, and Mn altered maternal and neonatal calf mineral status, but calf size and vigor at birth, passive transfer, and pre-weaning growth were not affected in this study.
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Affiliation(s)
- Emma L Stephenson
- Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
| | | | - Ann L Kenny
- Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
| | - Dusty W Nagy
- School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Brian M Shoemake
- School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Thomas B McFadden
- Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
| | | | - Allison M Meyer
- Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
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23
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Lubna S, Ahmad R. Clinical and biochemical understanding of Zinc interaction during liver diseases: A paradigm shift. J Trace Elem Med Biol 2023; 77:127130. [PMID: 36641955 DOI: 10.1016/j.jtemb.2023.127130] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/01/2022] [Accepted: 01/04/2023] [Indexed: 01/07/2023]
Abstract
Zinc (Zn) is an essential and the second most abundant trace element after Iron. It can apply antioxidant, anti-inflammatory, and anti-apoptotic activity. It is assumed to be indispensable for cell division, cellular differentiation and cell signalling. Zinc is essential for proper liver function which is also the site of its metabolism. Depleted Zn concentrations have been observed in both acute and chronic hepatic diseases. It is reported that Zn deficiency or abnormal Zn metabolism during majority of liver diseases is attributed to deficient dietary intake of Zn, augmented disposal of Zn in the urine, activation of certain Zn transporters, and expression of hepatic metallothionein. Undoubtedly, Zn is involved in generating many diseases but how and whether it plays role from acute to fulminant stage of all chronic liver diseases remains to be cleared. Here, we will discuss the role of Zn in development of different diseases specifically the involvement of Zn to understand the aetiology and intricate mechanism of dynamic liver diseases.
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Affiliation(s)
- Shiba Lubna
- Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202001, India
| | - Riaz Ahmad
- Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202001, India.
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24
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Ullah MI, Alameen AAM, Al-Oanzi ZH, Eltayeb LB, Atif M, Munir MU, Ejaz H. Biological Role of Zinc in Liver Cirrhosis: An Updated Review. Biomedicines 2023; 11:biomedicines11041094. [PMID: 37189711 DOI: 10.3390/biomedicines11041094] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/01/2023] [Accepted: 04/02/2023] [Indexed: 05/17/2023] Open
Abstract
Liver cirrhosis is a complication usually due to the consequence of persistent chronic liver disease. It is associated with different mechanisms, including hypoalbuminemia, impaired amino acid turnover, and micronutrient deficiencies. Consequently, cirrhotic patients can develop progressive complications like ascites, hepatic encephalopathy, and hepatocellular carcinoma. The liver is a vital organ that regulates the different metabolic pathways and transportation of trace elements. Zn is an indispensable micronutrient trace element involved in its crucial functions in cellular metabolic activity. Zn mediates its action by binding to a wide range of proteins; therefore, it imparts numerous biological effects, including cellular division, differentiation, and growth. It is also involved in critical processes for the biosynthesis of structural proteins and regulation of transcription factors and acts as a co-factor for the various enzymatic processes. As the liver is a significant regulator of Zn metabolism, its abnormalities lead to Zn deficiency, which has consequences on cellular, endocrine, immune, sensory, and skin dysfunctions. Conversely, Zn deficiency may modify the functions of hepatocytes and immune responses (acute phase protein production) in inflammatory liver diseases. This review has concisely stated the evolving indication of the critical role of Zn in biological processes and complications associated with liver cirrhosis pathogenesis due to Zn deficiency.
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Affiliation(s)
- Muhammad Ikram Ullah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
| | - Ayman Ali Mohammed Alameen
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
| | - Ziad H Al-Oanzi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
| | - Lienda Bashier Eltayeb
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdul Aziz University, Al-Kharj 11942, Riyadh, Saudi Arabia
| | - Muhammad Atif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
| | - Muhammad Usman Munir
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
| | - Hasan Ejaz
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Aljouf, Saudi Arabia
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25
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Kropp DR, Hodes GE. Sex differences in depression: An immunological perspective. Brain Res Bull 2023; 196:34-45. [PMID: 36863664 DOI: 10.1016/j.brainresbull.2023.02.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 02/05/2023] [Accepted: 02/27/2023] [Indexed: 03/04/2023]
Abstract
Depression is a heterogenous disorder with symptoms that present differently across individuals. In a subset of people depression is associated with alterations of the immune system that may contribute to disorder onset and symptomology. Women are twice as likely to develop depression and on average have a more sensitive adaptive and innate immune system when compared to men. Sex differences in pattern recognition receptors (PRRs), release of damage-associated molecular patterns (DAMPs), cell populations, and circulating cytokines play a critical role in inflammation onset. Sex differences in innate and adaptive immunity change the response of and repair to damage caused by dangerous pathogens or molecules in the body. This article reviews the evidence for sex specific immune responses that contribute to the sex differences in symptoms of depression that may account for the higher rate of depression in women.
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Affiliation(s)
- Dawson R Kropp
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Georgia E Hodes
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
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26
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Dalto DB, Audet I, Roy C, Deschêne K, Villeneuve G, Matte JJ, Lapointe J. Effects of dietary zinc/copper ratios on the metabolism of zinc and copper in weaned pigs. J Anim Sci 2023; 101:skad224. [PMID: 37392143 PMCID: PMC10424715 DOI: 10.1093/jas/skad224] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 06/28/2023] [Indexed: 07/03/2023] Open
Abstract
This study compared the effects of different dietary zinc/copper ratios on zinc (Zn) and copper (Cu) metabolism in weaned pigs. One hundred and sixty piglets (7.81 ± 0.25 kg; 21 d of age) were used in a completely randomized 2 × 2 factorial design composed with high (H) and low (L) levels of added dietary Zn (100 and 3,000 mg/kg) and dietary Cu (6 and 130 mg/kg). Piglets were slaughtered at 21, 28, 35, and 42 d of age for blood and tissues collection. Serum, jejunum mucosa, liver, and kidney concentrations of Zn and Cu were analyzed as well as tissues mRNA abundance of genes related to their metabolism. Serum and liver Zn concentrations increased at days 28, 35, and 42 in HZn groups compared to pre-treatment levels (day 21; P ≤ 0.01) but for LZn animals, values decreased at days 28, 35, and 42 in liver (P ≤ 0.01) but remained stable vs. day 21 levels in serum (P ≥ 0.37). Serum, jejunum mucosa, liver, and kidney Zn concentrations were greater in HZn groups from day 28 (P ≤ 0.01). In jejunum mucosa, the mRNA expression of ZIP4 was lower in HZn piglets at day 28 (P ≤ 0.01) and at day 42 whereas HCu supplementation increased ZIP4 expression in LZn but not in HZn diets (P = 0.05). For ZNT1, MT3, and MT1, values of relative mRNA expression were greater for HZn animals in jejunum mucosa, liver, and kidney (P ≤ 0.01) from day 28. In kidney (P < 0.01) at day 42, HZn supplementation increased MTs expression in both LCu or HCu groups. Serum and liver Cu concentrations decreased at days 35 and 42 in all treatments compared to day 21 (P ≤ 0.04), except LZnHCu in liver that was not different from day 21 (P ≥ 0.17). Serum Cu concentrations were lower in HZn and greater in HCu groups at days 35 and 42 (P ≤ 0.01) whereas hepatic Cu was reduced by HZn diets in both LCu and HCu groups at days 35 and 42 (P ≤ 0.01). Jejunum Cu concentrations were increased by HCu diets in HZn but not in LZn groups at days 28 and 42 (P ≤ 0.04). Renal Cu concentrations were greater in HZn groups at day 28 (P < 0.01) whereas at day 42 HZn diets increased Cu values in both LCu and HCu groups (P ≤ 0.01). The expression of ATP7A in kidney at day 42 was greater for HZn groups (P = 0.02). In conclusion, high dietary Zn levels were not efficiently regulated by homeostatic mechanisms and significantly impaired Cu homeostasis. Low dietary Zn/Cu ratios allow a more efficient regulation of the metabolism of these trace minerals in post-weaning piglets. The current official recommendations for Zn and Cu to post-weaning piglets apparently do not fulfill their requirements.
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Affiliation(s)
- Danyel Bueno Dalto
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
| | - Isabelle Audet
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
| | - Caroline Roy
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
| | - Karine Deschêne
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
| | - Geneviève Villeneuve
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
- Biology Department, Université de Sherbrooke, Sherbrooke, Quebec J1K 2R1, Canada
| | - J Jacques Matte
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
| | - Jérôme Lapointe
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada
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Rodrigues FAML, Sousa RDS, Minervino AHH, Oliveira FLCD, Sousa IKFD, Araújo CASC, Mori CS, Antonelli AC, Barrêto Júnior RA, Ortolani EL. Effects of Sodium Monensin on Copper Metabolism of Brazilian Santa Inês Sheep Submitted to Different Dietary Copper. Biol Trace Elem Res 2023; 201:196-203. [PMID: 35084633 DOI: 10.1007/s12011-022-03132-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 01/20/2022] [Indexed: 01/11/2023]
Abstract
This study aimed to evaluate the influence of sodium monensin on the hepatic accumulation of copper in sheep. Twenty-four Santa Inês crossbred sheep were used and allocated in a 2 × 2 factorial experiment with six repetitions and considering the factors dietary copper (basal and high) and supplementation (with and without sodium monensin). Thus, four homogeneous groups were formed: control (basal diet); monensin (Mon), 30 ppm of monensin; copper (Cu), 10 10 mg/kg BW per day of copper; monensin + copper (MonCu). The experimental period lasted 14 weeks. Liver and bile samples were collected at the beginning and end of the experiment to determine mineral element concentrations, and weekly blood samples for biochemical, hematological, and mineral evaluation. Liver copper concentrations at the beginning of the experiment did not vary between groups, while mean liver copper concentrations at the end of the experiment were higher in the MonCu, Cu, and Mon groups when compared to the control. At the end of the study, hepatic copper concentration was influenced by copper (p = 0.0001) and monensin (p = 0.0003) supplementation. Copper-supplemented groups had reduced liver iron contents (p = 0.0287) and increased copper concentrations in bile. The biochemical evaluation showed increased serum GGT and AST activity (p < 0.05) in the Cu and MonCu groups from the eleventh week on compared to the control and Mon groups. The increase in activity of these enzymes was influenced by copper supplementation (p = 0.0340). Monensin interferes positively with the hepatic accumulation of copper and the supplementation of this additive may predispose sheep to copper poisoning.
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Affiliation(s)
- Frederico Augusto Mazzocca Lopes Rodrigues
- Department of Clinical Science, College of Veterinary Medicine and Animal Science, University of Sao Paulo (FMVZ/USP), Av. Prof. Orlando Marques de Paiva, 87, Cidade Universitária, São Paulo, SP, CEP 05508-270, Brazil
| | - Rejane Dos Santos Sousa
- Institute of Studies of the Humid Tropic, Federal University of the South and Southeast of Pará, Rua Alberto Santos Dumont, s/n, Xinguara, 68557-335, Brazil
| | - Antonio Humberto Hamad Minervino
- Laboratory of Animal Health, LARSANA, Federal University of Western Pará, UFOPA, Rua Vera Paz, s/n, Salé, Santarém, PA, CEP 68040-255, Brazil.
| | - Francisco Leonado Costa de Oliveira
- Department of Clinical Science, College of Veterinary Medicine and Animal Science, University of Sao Paulo (FMVZ/USP), Av. Prof. Orlando Marques de Paiva, 87, Cidade Universitária, São Paulo, SP, CEP 05508-270, Brazil
| | - Isadora Karolina Freitas de Sousa
- Department of Clinical Science, College of Veterinary Medicine and Animal Science, University of Sao Paulo (FMVZ/USP), Av. Prof. Orlando Marques de Paiva, 87, Cidade Universitária, São Paulo, SP, CEP 05508-270, Brazil
| | - Carolina Akiko Sato Cabral Araújo
- Department of Veterinary Medicine, Federal Rural University of Pernambuco (UFRPE), Rua Manoel de Medeiros, s/n - Bairro Dois Irmãos, Recife, PE, CEP 52171-900, Brazil
| | - Clara Satsuki Mori
- Department of Clinical Science, College of Veterinary Medicine and Animal Science, University of Sao Paulo (FMVZ/USP), Av. Prof. Orlando Marques de Paiva, 87, Cidade Universitária, São Paulo, SP, CEP 05508-270, Brazil
| | - Alexandre Coutinho Antonelli
- Federal University of Vale do São Franciso (UNIVASF), Av. José de Sá Maniçoba, S/N - Centro, Petrolina, PE, CEP: 56304-917, Brazil
| | - Raimundo Alves Barrêto Júnior
- Department of Animal Science, Federal Rural University of the Semiarid Region (UFERSA), Av. Francisco Mota, s/nº - Bairro Pres. Costa e Silva, Mossoró, RN, CEP 59625-900, Brazil
| | - Enrico Lippi Ortolani
- Department of Clinical Science, College of Veterinary Medicine and Animal Science, University of Sao Paulo (FMVZ/USP), Av. Prof. Orlando Marques de Paiva, 87, Cidade Universitária, São Paulo, SP, CEP 05508-270, Brazil
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Maisonial-Besset A, Witkowski T, Quintana M, Besse S, Gaumet V, Cordonnier A, Alliot C, Vidal A, Denevault-Sabourin C, Tarrit S, Levesque S, Miot-Noirault E, Chezal JM. Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64Cu-Labelling of Immunoconjugates. Molecules 2022; 28:molecules28010075. [PMID: 36615280 PMCID: PMC9822305 DOI: 10.3390/molecules28010075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/12/2022] [Accepted: 12/17/2022] [Indexed: 12/24/2022] Open
Abstract
The development of 64Cu-based immuno-PET radiotracers requires the use of copper-specific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [64Cu]Cu-15-5 complex prompted us to investigate its potential for the 64Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA- and 15-5-mAb conjugates were radiolabelled with 64Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [64Cu]Cu-15-5- and [64Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88-94%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition.
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Affiliation(s)
- Aurélie Maisonial-Besset
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Tiffany Witkowski
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Mercedes Quintana
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Sophie Besse
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Vincent Gaumet
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Axel Cordonnier
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | | | | | - Caroline Denevault-Sabourin
- GICC EA7501, Team IMT, Université de Tours, UFR de Médecine, Bâtiment Vialle, 10 Boulevard Tonnellé, BP 3223, CEDEX 01, 37032 Tours, France
| | - Sébastien Tarrit
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Sophie Levesque
- Department of Nuclear Medicine, Jean Perrin Comprehensive Cancer Centre, F-63011 Clermont-Ferrand, France
| | - Elisabeth Miot-Noirault
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
| | - Jean-Michel Chezal
- Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, France
- Correspondence:
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Rodriguez-Sevilla JJ, Calvo X, Arenillas L. Causes and Pathophysiology of Acquired Sideroblastic Anemia. Genes (Basel) 2022; 13:1562. [PMID: 36140729 PMCID: PMC9498732 DOI: 10.3390/genes13091562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/22/2022] [Accepted: 08/26/2022] [Indexed: 01/19/2023] Open
Abstract
The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by anemia and the presence of ring sideroblasts in the bone marrow. Ring sideroblasts are abnormal erythroblasts with iron-loaded mitochondria that are visualized by Prussian blue staining as a perinuclear ring of green-blue granules. The mechanisms that lead to the ring sideroblast formation are heterogeneous, but in all of them, there is an abnormal deposition of iron in the mitochondria of erythroblasts. Congenital sideroblastic anemias include nonsyndromic and syndromic disorders. Acquired sideroblastic anemias include conditions that range from clonal disorders (myeloid neoplasms as myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms with ring sideroblasts) to toxic or metabolic reversible sideroblastic anemia. In the last 30 years, due to the advances in genomic techniques, a deep knowledge of the pathophysiological mechanisms has been accomplished and the bases for possible targeted treatments have been established. The distinction between the different forms of sideroblastic anemia is based on the study of the characteristics of the anemia, age of diagnosis, clinical manifestations, and the performance of laboratory analysis involving genetic testing in many cases. This review focuses on the differential diagnosis of acquired disorders associated with ring sideroblasts.
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Affiliation(s)
| | - Xavier Calvo
- Laboratori de Citologia Hematològica, Department of Pathology, Hospital del Mar, 08003 Barcelona, Spain
- Group of Translational Research on Hematological Neoplasms (GRETNHE), IMIM-Hospital del Mar, 08003 Barcelona, Spain
| | - Leonor Arenillas
- Laboratori de Citologia Hematològica, Department of Pathology, Hospital del Mar, 08003 Barcelona, Spain
- Group of Translational Research on Hematological Neoplasms (GRETNHE), IMIM-Hospital del Mar, 08003 Barcelona, Spain
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Munk DE, Lund Laursen T, Teicher Kirk F, Vilstrup H, Ala A, Gormsen LC, Ott P, Damgaard Sandahl T. Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study. Sci Rep 2022; 12:14714. [PMID: 36038585 PMCID: PMC9424214 DOI: 10.1038/s41598-022-18872-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/22/2022] [Indexed: 11/26/2022] Open
Abstract
Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson’s disease (WD). We used copper-64 (64Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic 64Cu content after oral 64Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols. The WD standard treatment zinc acetate 50 mg × 3 reduced the hepatic 64Cu content from 26.9 ± 7.5% to 13.3 ± 5.6% of the administered 64Cu. Zinc gluconate 50 mg × 3 was noninferior (P = 0.02) (35.8 ± 9.0% to 17.4 ± 7.5%). Zinc acetate 150 mg × 1 (33.1 ± 9.9% to 17.4 ± 7.5%) and zinc gluconate 150 mg × 1 (28.1 ± 6.7% to 22.0 ± 6.7%) were less effective. These effects were intra- and inter-individually highly variable, and 14% had no effect of any zinc regimen, which may explain disparities in zinc treatment efficacy in WD patients.
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Affiliation(s)
- Ditte Emilie Munk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark.
| | - Tea Lund Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark
| | - Frederik Teicher Kirk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark
| | - Aftab Ala
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
| | - Lars Christian Gormsen
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus, Denmark
| | - Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark
| | - Thomas Damgaard Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark
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Roy C, Avril S, Legendre C, Lelièvre B, Vellenriter H, Boni S, Cayon J, Guillet C, Guilloux Y, Chérel M, Hindré F, Garcion E. A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation. BMC Cancer 2022; 22:843. [PMID: 35918659 PMCID: PMC9347084 DOI: 10.1186/s12885-022-09808-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/16/2022] [Indexed: 11/08/2022] Open
Abstract
Background Glioblastoma (GB) is the most common and most aggressive malignant brain tumor. In understanding its resistance to conventional treatments, iron metabolism and related pathways may represent a novel avenue. As for many cancer cells, GB cell growth is dependent on iron, which is tightly involved in red-ox reactions related to radiotherapy effectiveness. From new observations indicating an impact of RX radiations on the expression of ceruloplasmin (CP), an important regulator of iron metabolism, the aim of the present work was to study the functional effects of constitutive expression of CP within GB lines in response to beam radiation depending on the oxygen status (21% O2 versus 3% O2). Methods and results After analysis of radiation responses (Hoechst staining, LDH release, Caspase 3 activation) in U251-MG and U87-MG human GB cell lines, described as radiosensitive and radioresistant respectively, the expression of 9 iron partners (TFR1, DMT1, FTH1, FTL, MFRN1, MFRN2, FXN, FPN1, CP) were tested by RTqPCR and western blots at 3 and 8 days following 4 Gy irradiation. Among those, only CP was significantly downregulated, both at transcript and protein levels in the two lines, with however, a weaker effect in the U87-MG, observable at 3% O2. To investigate specific role of CP in GB radioresistance, U251-MG and U87-MG cells were modified genetically to obtain CP depleted and overexpressing cells, respectively. Manipulation of CP expression in GB lines demonstrated impact both on cell survival and on activation of DNA repair/damage machinery (γH2AX); specifically high levels of CP led to increased production of reactive oxygen species, as shown by elevated levels of superoxide anion, SOD1 synthesis and cellular Fe2 + . Conclusions Taken together, these in vitro results indicate for the first time that CP plays a positive role in the efficiency of radiotherapy on GB cells. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09808-6.
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Affiliation(s)
- Charlotte Roy
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France
| | - Sylvie Avril
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France
| | - Claire Legendre
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France
| | - Bénédicte Lelièvre
- Centre Régional de Pharmacovigilance, Laboratoire de Pharmacologie-Toxicologie, CHU Angers, 4 rue Larrey, F-49100, Angers, France
| | - Honorine Vellenriter
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France
| | - Sébastien Boni
- Université d'Angers, SFR ICAT, Lentivec, F-49000, Angers, France
| | - Jérôme Cayon
- Université d'Angers, SFR ICAT, PACeM, F-49000, Angers, France
| | | | - Yannick Guilloux
- Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, F-44000, Nantes, France
| | - Michel Chérel
- Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, F-44000, Nantes, France
| | - François Hindré
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France.,Université d'Angers, SFR ICAT, PRIMEX, F-49000, Angers, France
| | - Emmanuel Garcion
- Université d'Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France. .,Université d'Angers, SFR ICAT, PACeM, F-49000, Angers, France. .,Université d'Angers, SFR ICAT, PRIMEX, F-49000, Angers, France. .,GLIAD - Design and Application of Innovative Local Treatments in Glioblastoma, CRCI2NA, Team 5, Inserm UMR 1307, CNRS UMR 6075, Institut de Biologie en Santé (IBS) - CHU, 4 rue Larrey, Angers, France.
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Brugger D, Wagner B, Windisch WM, Schenkel H, Schulz K, Südekum KH, Berk A, Pieper R, Kowalczyk J, Spolders M. Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety. Animal 2022; 16:100598. [PMID: 35952480 DOI: 10.1016/j.animal.2022.100598] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/24/2022] [Accepted: 06/28/2022] [Indexed: 11/01/2022] Open
Abstract
Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.
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Affiliation(s)
- D Brugger
- Institute of Animal Nutrition and Dietetics, Vetsuisse-Faculty, University of Zurich, Winterthurerstrasse 270, 8057 Zurich, Switzerland
| | - B Wagner
- BfR-Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
| | - W M Windisch
- Chair of Animal Nutrition, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Liesel-Beckmann-Strasse 2, 85354 Freising, Germany
| | - H Schenkel
- Institute of Animal Science, University of Hohenheim, Emil-Wolff-Strasse 12, 70599 Stuttgart, Germany
| | - K Schulz
- BfR-Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
| | - K-H Südekum
- Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany
| | - A Berk
- Institute of Animal Nutrition, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Bundesallee 37, 38116 Braunschweig, Germany
| | - R Pieper
- BfR-Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
| | - J Kowalczyk
- BfR-Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
| | - M Spolders
- BfR-Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
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Broiler responses to copper levels and sources: growth, tissue mineral content, antioxidant status and mRNA expression of genes involved in lipid and protein metabolism. BMC Vet Res 2022; 18:223. [PMID: 35698226 PMCID: PMC9195228 DOI: 10.1186/s12917-022-03286-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 05/10/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Five hundred 8-d old male broilers Cobb500 were randomly allotted into 10 treatments in factorial arrangement with 5 Cu levels (0, 4, 8, 12, and 16 mg/kg), and 2 sources (Cu proteinate, CuPro and Cu sulphate, CuSO4.5H2O) for a 10-d-experiment. RESULTS Feed conversion ratio (FCR) was better (P < 0.05) in CuPro fed chicks compared with CuSO4.5H2O group. Average daily feed intake (ADFI) decreased linearly (P < 0.05) as dietary Cu increased. A quadratic response (P < 0.05) to Cu levels was found for FCR, being optimized at 9.87 and 8.84 mg Cu/kg in CuPro and CuSO4.5H2O diets, respectively. Copper supplementation linearly increased liver Cu content (P < 0.05) and tended to linearly increase (P = 0.07) phosphorus (P) and copper in tibia. Manganese and zinc were higher (P < 0.05) in tibia of CuPro fed birds. Broilers fed CuPro exhibited lower liver iron (P < 0.05) content, lower activities of Cu, Zn superoxide dismutase (CuZnSOD) in breast muscle and liver, and glutathione peroxidase in liver. Glutathione peroxidase reduced linearly (P < 0.05) with CuPro levels and increased linearly (P < 0.05) with CuSO4.5H2O levels and were lower (P < 0.05) in all CuPro levels in breast muscle. Breast muscle malondialdehyde concentration tended to be higher (P = 0.08) in broilers fed CuSO4.5H2O. Copper levels linearly increased (P < 0.05) metallothionein (MT) and malate dehydrogenase (MDH) expression in liver, and six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) in the intestine. Copper elicited a quadratic response (P < 0.050) in AKT-1 and mammalian target of rapamycin (mTOR) in breast muscle, CuZnSOD in liver and antioxidant 1 copper chaperone (ATOX 1) in intestine. Broilers fed CuPro exhibited higher mRNA expression of mTOR in muscle breast and lower CuZnSOD in liver and ATOX 1 in intestine. Interaction (P < 0.05) between levels and sources was found in mRNA expression for GSK-3β, MT, and CuZnSOD in breast muscle, FAS and LPL in liver and MT and CTR1 in intestine. CONCLUSIONS CuPro showed beneficial effects on feed conversion and bone mineralization. Organic and inorganic Cu requirements are 9.87 and 8.84 mg Cu/kg, respectively.
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Massaccesi L, Galliera E, Pellegrini A, Banfi G, Corsi Romanelli MM. Osteomyelitis, Oxidative Stress and Related Biomarkers. Antioxidants (Basel) 2022; 11:antiox11061061. [PMID: 35739958 PMCID: PMC9220672 DOI: 10.3390/antiox11061061] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 12/30/2022] Open
Abstract
Bone is a very dynamic tissue, subject to continuous renewal to maintain homeostasis through bone remodeling, a process promoted by two cell types: osteoblasts, of mesenchymal derivation, are responsible for the deposition of new material, and osteoclasts, which are hematopoietic cells, responsible for bone resorption. Osteomyelitis (OM) is an invasive infectious process, with several etiological agents, the most common being Staphylococcus aureus, affecting bone or bone marrow, and severely impairing bone homeostasis, resulting in osteolysis. One of the characteristic features of OM is a strong state of oxidative stress (OS) with severe consequences on the delicate balance between osteoblastogenesis and osteoclastogenesis. Here we describe this, analyzing the effects of OS in bone remodeling and discussing the need for new, easy-to-measure and widely available OS biomarkers that will provide valid support in the management of the disease.
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Affiliation(s)
- Luca Massaccesi
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy; (E.G.); (M.M.C.R.)
- Correspondence: ; Tel.: +39-0250316027
| | - Emanuela Galliera
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy; (E.G.); (M.M.C.R.)
- IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy;
| | - Antonio Pellegrini
- Centre for Reconstructive Surgery and Osteoarticular Infections, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy;
| | - Giuseppe Banfi
- IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, Italy;
| | - Massimiliano Marco Corsi Romanelli
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy; (E.G.); (M.M.C.R.)
- Service of Laboratory Medicine1-Clinical Pathology, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
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Lynch EN, Campani C, Innocenti T, Dragoni G, Forte P, Galli A. Practical insights into chronic management of hepatic Wilson’s disease. World J Clin Cases 2022; 10:4334-4347. [PMID: 35663095 PMCID: PMC9125272 DOI: 10.12998/wjcc.v10.i14.4334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/07/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Wilson’s disease (WD) is a rare inherited disorder of human copper metabolism, with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations. In healthy individuals, the bile is the main route of elimination of copper. In WD patients, copper accumulates in the liver, it is released into the bloodstream, and is excreted in urine. Copper can also be accumulated in the brain, kidneys, heart, and osseous matter and causes damage due to direct toxicity or oxidative stress. Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood. Adherent, non-cirrhotic WD patients seem to have a normal life expectancy. Nevertheless, chronic management of patients with Wilson’s disease is challenging, as available biochemical tests have many limitations and do not allow a clear identification of non-compliance, overtreatment, or treatment goals. To provide optimal care, clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment. The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD. In particular, it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment. It also analyses available evidence on pregnancy and the role of low-copper diet in WD. Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.
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Affiliation(s)
- Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Paolo Forte
- Division of Gastroenterology, University Hospital “Careggi”, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Copper exposure for 30 days at a daily dose twice the recommended increases blood pressure and cardiac contractility. Life Sci 2022; 300:120579. [PMID: 35489564 DOI: 10.1016/j.lfs.2022.120579] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 11/21/2022]
Abstract
Copper is an essential factor for the body's homeostasis. However, excess copper compromises organic functions. AIMS We investigated the effects of copper exposure for 30 days on blood pressure (BP) and cardiac contractility and the putative involvement of nitric oxide (NO) and reactive oxygen species. MAIN METHODS Wistar rats (12 weeks old, 280 g) were randomized to the treated group that was exposed for 30 days to copper (2000 μg/kg/day CuCl2) and the control (Ct) group that received intraperitoneal saline (0.9%). KEY FINDINGS The blood concentration of copper was ~1.26 μg/mL in the copper-exposed group and ~0.024 μg/mL in the Ct group. The main metal accumulations occurred in the liver and kidneys. Copper exposure increased systolic BP (Cu: 141 ± 3 mmHg; Ct: 133 ± 3 mmHg) (tail cuff method), left ventricular systolic pressure and papillary muscle force. Calcium release from the sarcoplasmic reticulum was reduced. The contractile response to Ca2+ was increased by copper, and the effect was not altered by L-NAME. Copper increased contractions dependent on sarcolemmal Ca2+ influx, and this effect was not altered by L-NAME. The percentage response to isoproterenol decreased in the copper-exposed group, but L-NAME did not alter this reduction. Papillary force development at the peak and plateau of tetanic contractions also increased after copper exposure, but this effect was not altered by L-NAME. In situ detection of OH local production increased. SIGNIFICANCE Copper increased BP and cardiac force, increased Ca2+ inflow, reduced Ca2+ reuptake by the sarcoplasmic reticulum, and increased OH local production. Copper exposure at doses considered tolerable affects cardiac contractility.
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Fleming KM, Dargan PI, Massie J, Hodby K. Bicytopenia and neurological defects caused by zinc toxicity. Br J Haematol 2022; 198:e14-e17. [PMID: 35348202 DOI: 10.1111/bjh.18171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Kathryn M Fleming
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.,Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Paul I Dargan
- Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Jonathan Massie
- Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Katharine Hodby
- Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
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Ren P, Chen J, Hancock D, Vazquez-Añón M. Interactive Effects of Copper Sources and a High Level of Phytase in Phosphorus-Deficient Diets on Growth Performance, Nutrient Digestibility, Tissue Mineral Concentrations, and Plasma Parameters in Nursery Pigs. Biol Trace Elem Res 2021; 199:4582-4592. [PMID: 33432510 PMCID: PMC8516757 DOI: 10.1007/s12011-021-02580-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/05/2021] [Indexed: 11/12/2022]
Abstract
The present study investigated the interactive effects of copper sources and a high level of phytase on growth performance, nutrient digestibility, tissue mineral concentrations, and plasma parameters in nursery pigs. Weaning piglets (N = 192; 6.06 ± 0.99 kg), blocked by body weight, were randomly allotted to 1 of 4 dietary treatments, with 12 pens per treatment and 4 pigs per pen. A basal diet for each phase was formulated to meet nutrient requirements for nursery pigs with the exception that standardized total tract digestibility (STTD) P was reduced by 0.12% and Ca was adjusted to achieve Ca/STTD P = 2.15. The 4 dietary treatments were arranged in a 2 × 2 factorial design, with 2 Cu sources (125 mg/kg Cu from copper methionine hydroxy analogue chelate (Cu-MHAC) or copper sulfate (CuSO4)) and 2 phytase levels (0 or 1500 phytase units (FTU)/kg). Results showed that there was an interaction (P < 0.05) between Cu sources and phytase on ADG during days 0-41. When phytase was not present in the diets (P deficient), there was no difference between the two Cu sources in terms of ADG during days 0-41, whereas with phytase in the diets, Cu-MHAC tended to improve (P < 0.10) ADG during days 0-41 compared with CuSO4. Pigs fed Cu-MHAC had greater apparent total tract digestibility (ATTD) of neutral and acid detergent fiber and STTD of P than those fed CuSO4. Phytase increased (P < 0.05) growth performance, ATTD of Ca and P, and plasma inositol and growth hormone concentrations. In conclusion, Cu-MHAC may be more effective in improving growth rate than CuSO4 when phytase was supplemented at 1500 FTU/kg. Cu-MHAC enhanced fiber and P digestibility regardless of phytase, compared with CuSO4. Phytase addition in P-deficient diets was effective in improving growth performance, Ca and P digestibility, and plasma inositol and growth hormone concentrations.
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Affiliation(s)
- Ping Ren
- Novus International, Inc., St. Charles, MO, 63304, USA.
| | - Juxing Chen
- Novus International, Inc., St. Charles, MO, 63304, USA
| | - Deana Hancock
- Novus International, Inc., St. Charles, MO, 63304, USA
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Singh SB, Lin HC. Role of Intestinal Alkaline Phosphatase in Innate Immunity. Biomolecules 2021; 11:biom11121784. [PMID: 34944428 PMCID: PMC8698947 DOI: 10.3390/biom11121784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 11/23/2021] [Accepted: 11/23/2021] [Indexed: 12/14/2022] Open
Abstract
Intestinal alkaline phosphatase (IAP) is a multi-functional protein that has been demonstrated to primarily protect the gut. The role of IAP in maintaining intestinal homeostasis is underscored by the observation that IAP expression is defective in many gastrointestinal-related disorders such as inflammatory bowel disease IBD, necrotizing enterocolitis, and metabolic syndrome and that exogenous IAP supplementation improves the outcomes associated with these disorders. Additionally, studies using transgenic IAP-knock out (IAP-KO) mouse models further support the importance of the defensive role of IAP in the intestine. Supplementation of exogenous IAP and cellular overexpression of IAP have also been used in vitro to dissect out the downstream mechanisms of this protein in mammalian cell lines. Some of the innate immune functions of IAP include lipopolysaccharide (LPS) detoxification, protection of gut barrier integrity, regulation of gut microbial communities and its anti-inflammatory roles. A novel function of IAP recently identified is the induction of autophagy. Due to its critical role in the gut physiology and its excellent safety profile, IAP has been used in phase 2a clinical trials for treating conditions such as sepsis-associated acute kidney injury. Many excellent reviews discuss the role of IAP in physiology and pathophysiology and here we extend these to include recent updates on this important host defense protein and discuss its role in innate immunity via its effects on bacteria as well as on host cells. We will also discuss the relationship between IAP and autophagy and how these two pathways may act in concert to protect the gut.
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Affiliation(s)
- Sudha B. Singh
- Biomedical Research Institute of New Mexico, Albuquerque, NM 87108, USA;
| | - Henry C. Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA
- Correspondence:
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Seetharaman J, Sarma MS. Chelation therapy in liver diseases of childhood: Current status and response. World J Hepatol 2021; 13:1552-1567. [PMID: 34904029 PMCID: PMC8637676 DOI: 10.4254/wjh.v13.i11.1552] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/07/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson’s disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.
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Affiliation(s)
- Jayendra Seetharaman
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Shkembi B, Huppertz T. Influence of Dairy Products on Bioavailability of Zinc from Other Food Products: A Review of Complementarity at a Meal Level. Nutrients 2021; 13:4253. [PMID: 34959808 PMCID: PMC8705257 DOI: 10.3390/nu13124253] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/24/2021] [Accepted: 11/25/2021] [Indexed: 11/16/2022] Open
Abstract
In this paper, we reviewed the role of dairy products in dietary zinc absorption. Dairy products can have a reasonable contribution for dietary zinc intake in Western diets, where dairy consumption is high. However, the co-ingestion of dairy products can also improve zinc absorption from other food products. Such improvements have been observed when dairy products (e.g., milk or yoghurt) were ingested together with food such as rice, tortillas or bread products, all of which are considered to be high-phytate foods with low inherent zinc absorption. For foods low in phytate, the co-ingestion of dairy products did not improve zinc absorption. Improved zinc absorption of zinc from high-phytate foods following co-ingestion with dairy products may be related to the beneficial effects of the citrate and phosphopeptides present in dairy products. Considering that the main dietary zinc sources in areas in the world where zinc deficiency is most prevalent are typically high in phytate, the inclusion of dairy products in meals may be a viable dietary strategy to improve zinc absorption.
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Affiliation(s)
- Blerina Shkembi
- Food Quality & Design Group, Wageningen University & Research, 6708 PB Wageningen, The Netherlands;
| | - Thom Huppertz
- Food Quality & Design Group, Wageningen University & Research, 6708 PB Wageningen, The Netherlands;
- FrieslandCampina, 3818 LE Amersfoort, The Netherlands
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Grüngreiff K, Gottstein T, Reinhold D, Blindauer CA. Albumin Substitution in Decompensated Liver Cirrhosis: Don't Forget Zinc. Nutrients 2021; 13:4011. [PMID: 34836265 PMCID: PMC8618355 DOI: 10.3390/nu13114011] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2-4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.
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Affiliation(s)
- Kurt Grüngreiff
- Clinic of Gastroenterology, City Hospital Magdeburg GmbH, 39130 Magdeburg, Germany;
| | - Thomas Gottstein
- Clinic of Gastroenterology, City Hospital Magdeburg GmbH, 39130 Magdeburg, Germany;
| | - Dirk Reinhold
- Medical Faculty, Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, 39120 Magdeburg, Germany;
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Lall SP, Kaushik SJ. Nutrition and Metabolism of Minerals in Fish. Animals (Basel) 2021; 11:ani11092711. [PMID: 34573676 PMCID: PMC8466162 DOI: 10.3390/ani11092711] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/06/2021] [Accepted: 09/13/2021] [Indexed: 12/26/2022] Open
Abstract
Simple Summary Our aim is to introduce the mineral nutrition of fish and explain the complexity of determining requirements for these elements, which are absorbed and excreted by the fish into the surrounding water. To date, only the requirements for nine minerals have been investigated. The review is focused on the absorption and the dietary factors that reduce their absorption from feed ingredients of plant and animal origin. Some diseases, such as cataracts, anemia and bone deformity, have been linked to dietary deficiency of minerals. Abstract Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis, either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.
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Affiliation(s)
- Santosh P. Lall
- National Research Council of Canada, Halifax, NS B3H 3Z1, Canada
- Correspondence: (S.P.L.); (S.J.K.)
| | - Sadasivam J. Kaushik
- Retd. INRA, 64310 St Pée sur Nivelle, France
- Ecoaqua Institute, Universidad de Las Palmas de Gran Canaria, 35214 Las Palmas, Spain
- Correspondence: (S.P.L.); (S.J.K.)
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Babak MV, Ahn D. Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance. Biomedicines 2021; 9:biomedicines9080852. [PMID: 34440056 PMCID: PMC8389626 DOI: 10.3390/biomedicines9080852] [Citation(s) in RCA: 116] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/13/2021] [Accepted: 07/16/2021] [Indexed: 12/29/2022] Open
Abstract
Copper (Cu) is a vital element required for cellular growth and development; however, even slight changes in its homeostasis might lead to severe toxicity and deleterious medical conditions. Cancer patients are typically associated with higher Cu content in serum and tumor tissues, indicating increased demand of cancer cells for this micronutrient. Cu is known to readily cycle between the +1 and +2 oxidation state in biological systems. The mechanism of action of Cu complexes is typically based on their redox activity and induction of reactive oxygen species (ROS), leading to deadly oxidative stress. However, there are a number of other biomolecular mechanisms beyond ROS generation that contribute to the activity of anticancer Cu drug candidates. In this review, we discuss how interfering with intracellular Cu balance via either diet modification or addition of inorganic Cu supplements or Cu-modulating compounds affects tumor development, progression, and sensitivity to treatment modalities. We aim to provide the rationale for the use of Cu-depleting and Cu-overloading conditions to generate the best possible patient outcome with minimal toxicity. We also discuss the advantages of the use of pre-formed Cu complexes, such as Cu-(bis)thiosemicarbazones or Cu-N-heterocyclic thiosemicarbazones, in comparison with the in situ formed Cu complexes with metal-binding ligands. In this review, we summarize available clinical and mechanistic data on clinically relevant anticancer drug candidates, including Cu supplements, Cu chelators, Cu ionophores, and Cu complexes.
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Messersmith EM, Smerchek DT, Hansen SL. The Crossroads between Zinc and Steroidal Implant-Induced Growth of Beef Cattle. Animals (Basel) 2021; 11:1914. [PMID: 34199133 PMCID: PMC8300159 DOI: 10.3390/ani11071914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/24/2021] [Accepted: 06/24/2021] [Indexed: 12/17/2022] Open
Abstract
Growth-promoting technologies such as steroidal implants have been utilized in the beef industry for over 60 years and remain an indispensable tool for improving economic returns through consistently improved average daily gain via increased skeletal muscle hypertrophy. Zinc has been implicated in skeletal muscle growth through protein synthesis, satellite cell function, and many other growth processes. Therefore, the objective of this review was to present the available literature linking Zn to steroidal implant-induced protein synthesis and other metabolic processes. Herein, steroidal implants and their mode of action, the biological importance of Zn, and several connections between steroidal implants and Zn related to growth processes are discussed. These include the influence of Zn on hormone receptor signaling, circulating insulin-like growth factor-1 concentrations, glucose metabolism, protein synthesis via mTOR, and satellite cell proliferation and differentiation. Supplemental Zn has also been implicated in improved growth rates of cattle utilizing growth-promoting technologies, and steroidal implants appear to alter liver and circulating Zn concentrations. Therefore, this review provides evidence of the role of Zn in steroidal implant-induced growth yet reveals gaps in the current knowledge base related to optimizing Zn supplementation strategies to best capture growth performance improvements offered through steroidal implants.
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Affiliation(s)
| | | | - Stephanie L. Hansen
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA; (E.M.M.); (D.T.S.)
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Pabis K, Chiari Y, Sala C, Straka E, Giacconi R, Provinciali M, Li X, Brown-Borg H, Nowikovsky K, Valencak TG, Gundacker C, Garagnani P, Malavolta M. Elevated metallothionein expression in long-lived species mediates the influence of cadmium accumulation on aging. GeroScience 2021; 43:1975-1993. [PMID: 34117600 DOI: 10.1007/s11357-021-00393-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 05/24/2021] [Indexed: 11/29/2022] Open
Abstract
Cadmium (Cd) accumulates with aging and is elevated in long-lived species. Metallothioneins (MTs), small cysteine-rich proteins involved in metal homeostasis and Cd detoxification, are known to be related to longevity. However, the relationship between Cd accumulation, the role of MTs, and aging is currently unclear. Specifically, we do not know if long-lived species evolved an efficient metal stress response by upregulating their MT levels to reduce the toxic effects of environmental pollutants, such as Cd, that accumulate over their longer life span. It is also unknown if the number of MT genes, their expression, or both protect the organisms from potentially damaging effects during aging. To address these questions, we reanalyzed several cross-species studies and obtained data on MT expression and Cd accumulation in long-lived mouse models. We confirmed a relationship between species maximum life span in captive mammals and their Cd content in liver and kidney. We found that although the number of MT genes does not affect longevity, gene expression and protein amount of specific MT paralogs are strongly related to life span in mammals. MT expression rather than gene number may influence the high Cd levels and longevity of some species. In support of this, we found that overexpression of MT-1 accelerated Cd accumulation in mice and that tissue Cd was higher in long-lived mouse strains with high MT expression. We conclude that long-lived species have evolved a more efficient stress response by upregulating the expression of MT genes in presence of Cd, which contributes to elevated tissue Cd levels.
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Affiliation(s)
- Kamil Pabis
- Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Wien, Vienna, Austria
| | - Ylenia Chiari
- Department of Biology, George Mason University, Fairfax, VA, 22030, USA
| | - Claudia Sala
- Department of Physics and Astronomy, University of Bologna, 40126, Bologna, Italy
| | - Elisabeth Straka
- Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Wien, Vienna, Austria
| | - Robertina Giacconi
- Advanced Technology Center for Aging Research, IRCCS INRCA, 60121, Ancona, Italy
| | - Mauro Provinciali
- Advanced Technology Center for Aging Research, IRCCS INRCA, 60121, Ancona, Italy
| | - Xinna Li
- Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - Holly Brown-Borg
- Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58203, USA
| | - Karin Nowikovsky
- Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Teresa G Valencak
- Department of Animal Science and Technology, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China
| | - Claudia Gundacker
- Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Wien, Vienna, Austria
| | - Paolo Garagnani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), and Interdepartmental Centre "L. Galvani" (CIG), University of Bologna, Bologna, Italy.,Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Marco Malavolta
- Advanced Technology Center for Aging Research, IRCCS INRCA, 60121, Ancona, Italy.
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Sipos AG, Pákozdy K, Jäger S, Larson K, Takacs P, Kozma B. Fractional CO 2 laser treatment effect on cervicovaginal lavage zinc and copper levels: a prospective cohort study. BMC WOMENS HEALTH 2021; 21:235. [PMID: 34092217 PMCID: PMC8180012 DOI: 10.1186/s12905-021-01379-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 05/24/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND The basic principle of vaginal laser therapy is the rejuvenation of the affected tissue. Zinc and copper are essential nutritional trace elements and have a key role in connective tissue homeostasis. We aimed to investigate the effect of vaginal, fractional CO2 laser treatment on cervicovaginal lavage (CVL) zinc and copper levels. METHODS Twenty-nine postmenopausal women with symptoms of vaginal dryness were enrolled in our prospective cohort study. Three treatments with MonaLisa Touch CO2 laser system were performed four weeks apart. At each treatment CVL was collected, Vaginal Health Index (VHI) was obtained, and Visual Analog Scale (VAS) for vaginal dryness was assigned by patients. Zinc and copper concentrations were measured with optical emission spectrometry before each treatment and six weeks after the 3rd treatment. RESULTS The VHI scores significantly improved after each laser treatment (mean ± SD VHI score, 13.03 ± 4.49 before vs. 15.55 ± 4.35 after the 1st, 17.79 ± 4.57 after the 2nd and 19.38 ± 4.39 after the 3rd treatment, P < 0.01). Similarly, VAS scores reflected improvement (mean ± SD VAS score 6.59 ± 2.86 before vs. 4.17 ± 2.86 after the 1st, 2.45 ± 2.43 after the 2nd and 1.41 ± 1.94 after the 3rd treatment, P < 0.01). CVL zinc levels were significantly higher compared to copper levels (0.06 ± 0.04 vs. 0.006 ± 0.006 mg/L, P < 0.01) at baseline. While copper levels remained the same through treatments, the CVL zinc level was significantly higher after the second laser treatment compared to the baseline. CONCLUSIONS Fractional CO2 laser treatment of the vagina impacts CVL zinc and copper levels differently. While CVL copper levels were not different after each laser treatment, zinc levels were significantly higher after the second treatment before returning to baseline values.
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Affiliation(s)
- Attila G Sipos
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 98. Nagyerdei krt., Debrecen, 4032, Hungary
| | - Krisztina Pákozdy
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 98. Nagyerdei krt., Debrecen, 4032, Hungary
| | - Szilvia Jäger
- Fempharma Ltd, Vígkedvű Mihály utca 21. 2/5., Debrecen, 4024, Hungary
| | - Kindra Larson
- Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 526, Norfolk, VA, 23507-2007, USA
| | - Peter Takacs
- Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 526, Norfolk, VA, 23507-2007, USA
| | - Bence Kozma
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 98. Nagyerdei krt., Debrecen, 4032, Hungary.
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Piacenza F, Giacconi R, Costarelli L, Basso A, Bürkle A, Moreno-Villanueva M, Dollé MET, Jansen E, Grune T, Weber D, Stuetz W, Gonos ES, Schön C, Bernhardt J, Grubeck-Loebenstein B, Sikora E, Toussaint O, Debacq-Chainiaux F, Franceschi C, Capri M, Hervonen A, Hurme M, Slagboom E, Breusing N, Mocchegiani E, Malavolta M. Age, sex and BMI influence on copper, zinc and their major serum carrier proteins in a large European population including Nonagenarian Offspring from MARK-AGE study. J Gerontol A Biol Sci Med Sci 2021; 76:2097-2106. [PMID: 33983441 DOI: 10.1093/gerona/glab134] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Indexed: 11/12/2022] Open
Abstract
The analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of metals (metallostasis). However, their relationship with aging, sex, BMI, as well as with nutritional and inflammatory markers was never investigated in a large-scale study. Here, we report results from the European large-scale cross-sectional study MARK-AGE in which Cu, Zn, Alb, Cp as well as nutritional and inflammatory parameters were determined in 2424 age-stratified subjects (35-75 years) including the general population (RASIG), nonagenarian offspring (GO), a well-studied genetic model of longevity, and spouses of GO (SGO). In RASIG, Cu to Zn ratio and Cp to Alb ratio were higher in women than in men. Both ratios increased with aging because Cu and Cp increased and Alb and Zn decreased. Cu, Zn, Alb and Cp were found associated with several inflammatory as well as nutritional biomarkers.GO showed higher Zn levels and higher Zn to Alb ratio compared to RASIG, but we did not observe significant differences with SGO, likely as a consequence of the low sample size of SGO and the shared environment. Our results show that aging, sex, BMI and GO status are characterized by different levels of Cu, Zn and their serum carrier proteins. These data and their relationship with inflammatory biomarkers support the concept that loss of metallostasis is a characteristic of inflammaging.
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Affiliation(s)
- Francesco Piacenza
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | - Robertina Giacconi
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | - Laura Costarelli
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | - Andrea Basso
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | - Alexander Bürkle
- Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany
| | - María Moreno-Villanueva
- Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany.,Human Performance Research Centre, Department of Sport Science, University of Konstanz, Konstanz, Germany
| | - Martijn E T Dollé
- Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Eugène Jansen
- Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.,NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany
| | - Daniela Weber
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
| | - Wolfgang Stuetz
- Institute of Nutritional Sciences, University of Hohenheim, Stuttgart, Germany
| | - Efstathios S Gonos
- National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece
| | | | | | | | - Ewa Sikora
- Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
| | - Olivier Toussaint
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | | | - Claudio Franceschi
- Laboratory of Systems Medicine of Healthy Aging and Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, Russia. Lobachevsky State University of Nizhny Novgorod, Russia
| | - Miriam Capri
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.CIG-Interdepartmental Center "L. Galvani", Alma Mater Studiorum, University of Bologna, Bologna, Italy.,Interdepartmental Center "Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate)", Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | | | - Mikko Hurme
- Medical School, University of Tampere, Tampere, Finland
| | - Eline Slagboom
- Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Nicolle Breusing
- Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
| | - Eugenio Mocchegiani
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
| | - Marco Malavolta
- Translational Research Center of Nutrition and Ageing, IRCCS INRCA, Ancona, Italy
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