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Kępińska-Pacelik J, Biel W. Turmeric and Curcumin-Health-Promoting Properties in Humans versus Dogs. Int J Mol Sci 2023; 24:14561. [PMID: 37834009 PMCID: PMC10572432 DOI: 10.3390/ijms241914561] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/14/2023] [Accepted: 09/25/2023] [Indexed: 10/15/2023] Open
Abstract
The growing popularity of the use of nutraceuticals in the prevention and alleviation of symptoms of many diseases in humans and dogs means that they are increasingly the subject of research. A representative of the nutraceutical that deserves special attention is turmeric. Turmeric belongs to the family Zingiberaceae and is grown extensively in Asia. It is a plant used as a spice and food coloring, and it is also used in traditional medicine. The biologically active factors that give turmeric its unusual properties and color are curcuminoids. It is a group of substances that includes curcumin, de-methoxycurcumin, and bis-demethoxycurcumin. Curcumin is used as a yellow-orange food coloring. The most important pro-health effects observed after taking curcuminoids include anti-inflammatory, anticancer, and antioxidant effects. The aim of this study was to characterize turmeric and its main substance, curcumin, in terms of their properties, advantages, and disadvantages, based on literature data.
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Affiliation(s)
- Jagoda Kępińska-Pacelik
- Department of Monogastric Animal Sciences, Division of Animal Nutrition and Food, West Pomeranian University of Technology in Szczecin, Klemensa Janickiego 29, 71-270 Szczecin, Poland
| | - Wioletta Biel
- Department of Monogastric Animal Sciences, Division of Animal Nutrition and Food, West Pomeranian University of Technology in Szczecin, Klemensa Janickiego 29, 71-270 Szczecin, Poland
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2
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Calvet C, Seebeck P. What to consider for ECG in mice-with special emphasis on telemetry. Mamm Genome 2023; 34:166-179. [PMID: 36749381 PMCID: PMC10290603 DOI: 10.1007/s00335-023-09977-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 01/16/2023] [Indexed: 02/08/2023]
Abstract
Genetically or surgically altered mice are commonly used as models of human cardiovascular diseases. Electrocardiography (ECG) is the gold standard to assess cardiac electrophysiology as well as to identify cardiac phenotypes and responses to pharmacological and surgical interventions. A variety of methods are used for mouse ECG acquisition under diverse conditions, making it difficult to compare different results. Non-invasive techniques allow only short-term data acquisition and are prone to stress or anesthesia related changes in cardiac activity. Telemetry offers continuous long-term acquisition of ECG data in conscious freely moving mice in their home cage environment. Additionally, it allows acquiring data 24/7 during different activities, can be combined with different challenges and most telemetry systems collect additional physiological parameters simultaneously. However, telemetry transmitters require surgical implantation, the equipment for data acquisition is relatively expensive and analysis of the vast number of ECG data is challenging and time-consuming. This review highlights the limits of non-invasive methods with respect to telemetry. In particular, primary screening using non-invasive methods can give a first hint; however, subtle cardiac phenotypes might be masked or compensated due to anesthesia and stress during these procedures. In addition, we detail the key differences between the mouse and human ECG. It is crucial to consider these differences when analyzing ECG data in order to properly translate the insights gained from murine models to human conditions.
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Affiliation(s)
- Charlotte Calvet
- Zurich Integrative Rodent Physiology (ZIRP), University of Zurich, Zurich, Switzerland
| | - Petra Seebeck
- Zurich Integrative Rodent Physiology (ZIRP), University of Zurich, Zurich, Switzerland
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3
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Testing the Feasibility and Dietary Impact of Macaroni Fortified with Green Tea and Turmeric Curcumin Extract in Diabetic Rats. Foods 2023; 12:foods12030534. [PMID: 36766064 PMCID: PMC9914615 DOI: 10.3390/foods12030534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/14/2023] [Accepted: 01/16/2023] [Indexed: 01/27/2023] Open
Abstract
Macaroni is a commercially available Italian food product that is popular among consumers around the world. The supplementation of green tea extract (GTE) and turmeric curcumin extract (TCE) in macaroni may serve as promising and beneficial bioactive ingredients. We aimed to produce functional macaroni, assess the degree of consumer satisfaction and study the antidiabetic activity in diabetic rats. In this study, macaroni was fortified with GTE, TCE and a mixture of GTE and TCE ratio of 1:1, w/w (GTE/TCE). The resulting products were then analyzed in terms of their chemical compositions, while the degree of consumer satisfaction was monitored and the hypoglycemic and hypolipidemic effects in streptozotocin (STZ)-rats were investigated. GTE/TCE-M exhibited the strongest antioxidant activity (p < 0.05), while phenolics were most abundant in GTE-M. The overall preference for GTE-M, TCE-M and GTE/TCE-M were within ranges of 4.7-5.1, 5.9-6.7 and 6.2-8.2, respectively, in the nine-point hedonic scale. Consumption of these three preparations of macaroni (30 and 300 mg/kg each) neither decreased nor exacerbated increasing blood glucose levels in diabetic rats, while GTE-M (30 mg/kg) tended to lower increased serum triglyceride and cholesterol levels. In conclusion, GTE/TCE-M containing high amounts of bioactive EGCG and curcumin exerted the strongest degree of antioxidant activity and received the highest level of acceptance. Importantly, consumption of GTE-M tentatively ameliorated serum lipid abnormalities in diabetic STZ-induced rats by inhibiting lipase digestion and lipid absorption. Herein, we are proposing that GTE-fortified macaroni is a functional food that can mitigate certain metabolic syndromes.
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4
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Zhang L, Li C, Wang S, Avtanski D, Hadzi-Petrushev N, Mitrokhin V, Mladenov M, Wang F. Tetrahydrocurcumin-Related Vascular Protection: An Overview of the Findings from Animal Disease Models. Molecules 2022; 27:5100. [PMID: 36014335 PMCID: PMC9412611 DOI: 10.3390/molecules27165100] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/01/2022] [Accepted: 08/05/2022] [Indexed: 01/05/2023] Open
Abstract
Tetrahydrocurcumin (THC), one of the major metabolites of CUR, possesses several CUR-like pharmacological effects; however, its mechanisms of action are largely unknown. This manuscript aims to summarize the literature on the preventive role of THC on vascular dysfunction and the development of hypertension by exploring the effects of THC on hemodynamic status, aortic elasticity, and oxidative stress in vasculature in different animal models. We review the protective effects of THC against hypertension induced by heavy metals (cadmium and iron), as well as its impact on arterial stiffness and vascular remodeling. The effects of THC on angiogenesis in CaSki xenografted mice and the expression of vascular endothelial growth factor (VEGF) are well documented. On the other hand, as an anti-inflammatory and antioxidant compound, THC is involved in enhancing homocysteine-induced mitochondrial remodeling in brain endothelial cells. The experimental evidence regarding the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion injury and the therapeutic potential of THC to alleviate mitochondrial cerebral dysmorphic dysfunction patterns is also scrutinized and explored. Overall, the studies on different animal models of disease suggest that THC can be used as a dietary supplement to protect against cardiovascular changes caused by various factors (such as heavy metal overload, oxidative stress, and carcinogenesis). Additionally, the reviewed literature data seem to confirm THC's potential to improve mitochondrial dysfunction in cerebral vasculature during ischemic stroke through epigenetic mechanisms. We suggest that further preclinical studies should be implemented to demonstrate THC's vascular-protective, antiangiogenic, and anti-tumorigenic effects in humans. Applying the methods used in the presently reviewed studies would be useful and will help define the doses and methods of THC administration in various disease settings.
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Affiliation(s)
- Li Zhang
- Cancer Center, Department of Medical Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
| | - Changhu Li
- Cancer Center, Division of Radiation Physics, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Sicheng Wang
- Medical Department, 6th City Clinical Hospital, 220037 Minsk, Belarus
| | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, 110 E 59th Street, New York, NY 10022, USA
| | - Nikola Hadzi-Petrushev
- Faculty of Natural Sciences and Mathematics, Institute of Biology, “Ss. Cyril and Methodius” University, P.O. Box 162, 1000 Skopje, North Macedonia
| | - Vadim Mitrokhin
- Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova Street, 1, 117997 Moscow, Russia
| | - Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, “Ss. Cyril and Methodius” University, P.O. Box 162, 1000 Skopje, North Macedonia
- Department of Physiology, Pirogov Russian National Research Medical University, Ostrovityanova Street, 1, 117997 Moscow, Russia
| | - Feng Wang
- Cancer Center, Department of Medical Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
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Kumfu S, Chattipakorn SC, Chattipakorn N. Iron overload cardiomyopathy: Using the latest evidence to inform future applications. Exp Biol Med (Maywood) 2022; 247:574-583. [PMID: 35130741 DOI: 10.1177/15353702221076397] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Iron overload can be the result of either dysregulated iron metabolism in the case of hereditary hemochromatosis or repeated blood transfusions in the case of secondary hemochromatosis (e.g. in β-thalassemia and sickle cell anemia patients). Under iron overload conditions, transferrin (Tf) saturation leads to an increase in non-Tf bound iron which can result in the generation of reactive oxygen species (ROS). These excess ROS can damage cellular components, resulting in the dysfunction of vital organs including iron overload cardiomyopathy (IOC). Multiple studies have demonstrated that L-type and T-type calcium channels are the main routes for iron uptake in the heart, and that calcium channel blockers, given either individually or in combination with standard iron chelators, confer cardioprotective effects under iron overload conditions. Treatment with antioxidants may also provide therapeutic benefits. Interestingly, recent studies have suggested that mitochondrial dynamics and regulated cell death (RCD) pathways are potential targets for pharmacological interventions against iron-induced cardiomyocyte injury. In this review, the potential therapeutic roles of iron chelators, antioxidants, iron uptake/metabolism modulators, mitochondrial dynamics modulators, and inhibitors of RCD pathways in IOC are summarized and discussed.
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Affiliation(s)
- Sirinart Kumfu
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.,Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.,Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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6
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Settapramote N, Utama-ang N, Petiwathayakorn T, Settakorn K, Svasti S, Srichairatanakool S, Koonyosying P. Antioxidant Effects of Anthocyanin-Rich Riceberry™ Rice Flour Prepared Using Dielectric Barrier Discharge Plasma Technology on Iron-Induced Oxidative Stress in Mice. Molecules 2021; 26:4978. [PMID: 34443567 PMCID: PMC8399969 DOI: 10.3390/molecules26164978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/10/2021] [Accepted: 08/13/2021] [Indexed: 11/17/2022] Open
Abstract
Redox-active iron generates reactive oxygen species that can cause oxidative organ dysfunction. Thus, the anti-oxidative systems in the body and certain dietary antioxidants, such as anthocyanins, are needed to control oxidative stress. We aimed to investigate the effects of dielectric barrier discharge (DBD) plasma technology in the preparation of Riceberry™ rice flour (PRBF) on iron-induced oxidative stress in mice. PRBF using plasma technology was rich in anthocyanins, mainly cyanidine-3-glucoside and peonidine-3-glucoside. PRBF (5 mg AE/mg) lowered WBC numbers in iron dextran (FeDex)-loaded mice and served as evidence of the reversal of erythrocyte superoxide dismutase activity, plasma total antioxidant capacity, and plasma and liver thiobarbituric acid-reactive substances in the loading mice. Consequently, the PRBF treatment was observed to be more effective than NAC treatment. PRBF would be a powerful supplementary and therapeutic antioxidant product that is understood to be more potent than NAC in ameliorating the effects of iron-induced oxidative stress.
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Affiliation(s)
- Natwalinkhol Settapramote
- Division of Product Development Technology, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50200, Thailand; (N.S.); (N.U.-a.)
- Cluster of High Value Product from Thai Rice for Health, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Agro-Industry, Faculty of Agriculture and Technology, Surin Campus, Rajamangala University of Technology Isan, Surin 32000, Thailand
| | - Niramon Utama-ang
- Division of Product Development Technology, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50200, Thailand; (N.S.); (N.U.-a.)
- Cluster of High Value Product from Thai Rice for Health, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Touchwin Petiwathayakorn
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (S.S.)
| | - Kornvipa Settakorn
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (S.S.)
| | - Saovaros Svasti
- Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakorn Pathom 71300, Thailand;
| | - Somdet Srichairatanakool
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (S.S.)
| | - Pimpisid Koonyosying
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (T.P.); (K.S.); (S.S.)
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7
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Ávila RA, Rossi EM, de Carvalho GM, Krause M, Leopoldo AS, Carneiro MTWD, Dos Santos L. Moderate-intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats. Exp Physiol 2021; 106:1772-1784. [PMID: 34148259 DOI: 10.1113/ep089429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 06/17/2021] [Indexed: 12/24/2022]
Abstract
NEW FINDINGS What is the central question of this study? The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well-established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known. What is the main finding and its importance? Moderate-intensity aerobic training had benefits in a rodent model of iron-overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non-pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron-overloaded patients. ABSTRACT Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60-70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for iron-overload cardiomyopathy.
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Affiliation(s)
- Renata Andrade Ávila
- Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil.,Faculdades Integradas São Pedro (FAESA), Vitória, ES, Brazil
| | - Emilly Martinelli Rossi
- Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil
| | | | - Maiara Krause
- Department of Chemistry, Federal University of Espirito Santo, Vitória, ES, Brazil
| | | | | | - Leonardo Dos Santos
- Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil
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8
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Cotoraci C, Ciceu A, Sasu A, Hermenean A. Natural Antioxidants in Anemia Treatment. Int J Mol Sci 2021; 22:ijms22041883. [PMID: 33668657 PMCID: PMC7918704 DOI: 10.3390/ijms22041883] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/07/2021] [Accepted: 02/11/2021] [Indexed: 01/03/2023] Open
Abstract
Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.
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Affiliation(s)
- Coralia Cotoraci
- Department of Hematology, Faculty of Medicine, Vasile Goldis Western University of Arad, Rebreanu 86, 310414 Arad, Romania;
- Correspondence:
| | - Alina Ciceu
- “Aurel Ardelean” Institute of Life Sciences, Vasile Godis Western University of Arad, Rebreanu 86, 310414 Arad, Romania; (A.C.); (A.H.)
| | - Alciona Sasu
- Department of Hematology, Faculty of Medicine, Vasile Goldis Western University of Arad, Rebreanu 86, 310414 Arad, Romania;
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, Vasile Godis Western University of Arad, Rebreanu 86, 310414 Arad, Romania; (A.C.); (A.H.)
- Department of Histology, Faculty of Medicine, Vasile Goldis Western University of Arad, Rebreanu 86, 310414 Arad, Romania
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9
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Hatairaktham S, Masaratana P, Hantaweepant C, Srisawat C, Sirivatanauksorn V, Siritanaratkul N, Panichkul N, Kalpravidh RW. Curcuminoids supplementation ameliorates iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfusion-dependent β-thalassemia/Hb E patients. Ann Hematol 2021; 100:891-901. [PMID: 33388858 DOI: 10.1007/s00277-020-04379-7] [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: 08/03/2020] [Accepted: 12/16/2020] [Indexed: 10/22/2022]
Abstract
Curcuminoids, polyphenol compounds in turmeric, possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities. Effects of curcuminoids in thalassemia patients have been explored in a limited number of studies using different doses of curcuminoids. The present study aims to evaluate the effects of 24-week curcuminoids supplementation at the dosage of 500 and 1000 mg/day on iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfused β-thalassemia/Hb E patients. In general, both curcuminoids dosages significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in the patients. In contrast, reductions in iron parameter levels were more remarkable in the 1000 mg/day group. Subgroup analysis revealed that a marker of hypercoagulability was significantly decreased only in patients with baseline ferritin ≤ 1000 ng/ml independently of curcuminoids dosage. Moreover, the alleviation of iron loading parameters was more remarkable in patients with baseline ferritin > 1000 ng/ml who receive 1000 mg/day curcuminoids. On the other hand, the responses of oxidative stress markers were higher with 500 mg/day curcuminoids regardless of baseline ferritin levels. Our study suggests that baseline ferritin levels should be considered in the supplementation of curcuminoids and the appropriate curcuminoids dosage might differ according to the required therapeutic effect. Thai Clinical Trials Registry (TCTR): TCTR20200731003; July 31, 2020 "retrospectively registered".
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Affiliation(s)
- Suneerat Hatairaktham
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Patarabutr Masaratana
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
| | - Chattree Hantaweepant
- Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chatchawan Srisawat
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Vorapan Sirivatanauksorn
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Noppadol Siritanaratkul
- Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Narumol Panichkul
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Ruchaneekorn W Kalpravidh
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
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10
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Koonyosying P, Tantiworawit A, Hantrakool S, Utama-Ang N, Cresswell M, Fucharoen S, Porter JB, Srichairatanakool S. Consumption of a green tea extract-curcumin drink decreases blood urea nitrogen and redox iron in β-thalassemia patients. Food Funct 2020; 11:932-943. [PMID: 31950948 DOI: 10.1039/c9fo02424g] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The most important cause of death in β-thalassemia major patients is organ dysfunction due to iron deposits. Non-transferrin bound iron (NTBI), labile plasma iron (LPI) and labile iron pool are redox-active forms of iron found in thalassemia. Iron chelation therapy is adopted to counteract the resulting iron overload. Extracts of green tea (GTE) and curcumin exhibit iron-chelating and antioxidant activities in iron-loaded cells and β-thalassemic mice. We have used our GTE-CUR drink to investigate the potential amelioration of iron overload and oxidative stress in transfusion-dependent β-thalassemia (TDT) patients. The patients were enrolled for a control group without and with GTE-CUR treatments (17.3 and 35.5 mg EGCG equivalent). Along with regular chelation therapy, they were daily administered the drink for 60 d. Blood samples were collected at the beginning of the study and after 30 d and 60 d for biochemical and hematological tests. Interestingly, we found a decrease of blood urea nitrogen levels (P < 0.05), along with a tendency for a decrease of NTBI and LPI, and a delay in increasing lipid-peroxidation product levels in the GTE-CUR groups. The findings suggest that GTE-CUR could increase kidney function and diminish redox-active iron in iron overloaded β-thalassemia patients.
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Affiliation(s)
- Pimpisid Koonyosying
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
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11
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Lopresti AL. Association between Micronutrients and Heart Rate Variability: A Review of Human Studies. Adv Nutr 2020; 11:559-575. [PMID: 31942924 PMCID: PMC7231600 DOI: 10.1093/advances/nmz136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 12/05/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023] Open
Abstract
Heart rate variability (HRV) is a measure of the variation between consecutive heartbeats. It provides a marker of the interplay between the parasympathetic and sympathetic nervous systems, and there is an increasing body of evidence confirming an increased HRV is associated with better mental and physical health. HRV may be a useful marker of stress as it represents the ability of the heart to respond to a variety of physiological and environmental stimuli. HRV tends to decrease as we age and is positively associated with physical activity, fitness, and healthier lifestyles. The relation between HRV and micronutrients (vitamins and minerals) has also received some attention in the research literature. In this review, cross-sectional and interventional studies on human populations examining the relation between HRV and micronutrients are appraised. Micronutrients identified and examined in this review include vitamins D, B-12, C, and E; the minerals magnesium, iron, zinc, and coenzyme Q10; and a multivitamin-mineral formula. Due to the paucity of research and significant heterogeneity in studies, definitive conclusions about the effects of these micronutrients on HRV cannot be made at this time. However, there is accumulating evidence suggesting deficiencies in vitamins D and B-12 are associated with reduced HRV, and zinc supplementation during pregnancy can have positive effects on HRV in offspring up until the age of 5 y. To further elucidate the relation between micronutrients and HRV, additional robustly designed and adequately powered studies are required.
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Affiliation(s)
- Adrian L Lopresti
- College of Science, Health, Engineering, and Education, Murdoch University, Perth, Western Australia, Australia,Clinical Research Australia, Perth, Western Australia, Australia,Address correspondence to ALL (e-mail: )
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12
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Kumfu S, Chattipakorn S, Chattipakorn N. Antioxidant and chelator cocktails to prevent oxidative stress under iron-overload conditions. Pathology 2020. [DOI: 10.1016/b978-0-12-815972-9.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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13
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Yang X, Zhu X, Tang X, Liu M, Zheng H, Zheng L. Astragalus polysaccharides meliorate cardiovascular dysfunction in iron-overloaded thalassemic mice. Exp Biol Med (Maywood) 2019; 244:1202-1209. [PMID: 31514541 DOI: 10.1177/1535370219876540] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Affiliation(s)
- Xue Yang
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
| | - Xiaoxi Zhu
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
| | - Xianying Tang
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
| | - Mei Liu
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
| | - Huiling Zheng
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
| | - Lin Zheng
- Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, China
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Abstract
Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates. Recent studies have, however, suggested that it is iron overload in mitochondria that contributes to cellular oxidative stress, mitochondrial damage, cardiac arrhythmias, as well as the development of cardiomyopathy. Iron chelators, antioxidants, and/or calcium channel blockers have been demonstrated to prevent and ameliorate cardiac dysfunction in animal models as well as in patients suffering from cardiac iron overload. Hence, either a mono-therapy or combination therapies with any of the aforementioned agents may serve as a novel treatment in iron-overload patients in the near future. In the present article, we review the mechanisms of cytosolic and/or mitochondrial iron load in the heart which may contribute synergistically or independently to the development of iron-associated cardiomyopathy. We also review available as well as potential future novel treatments.
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Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, Gholami M, Mir SM. An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial. Phytother Res 2018; 32:1828-1835. [PMID: 29806132 DOI: 10.1002/ptr.6118] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 04/03/2018] [Accepted: 04/26/2018] [Indexed: 11/08/2022]
Abstract
This study investigated the effects of curcumin, the active polyphenol in turmeric, on iron overload, hepcidin level, and liver function in β-thalassemia major patients. This double-blind randomized controlled clinical trial was conducted on 68 β-thalassemia major patients. The subjects were randomly divided into 2 groups to receive either 500 mg curcumin capsules (total: 1,000 mg) twice daily or placebo for 12 weeks. Dietary intakes and biochemical variables including hemoglobin, transferrin saturation, total iron binding capacity, nontransferrin bound iron (NTBI), ferritin, hepcidin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed at the beginning and end of the trial. Curcumin significantly reduced serum levels of NTBI (2.83 ± 1.08 compared with 2.22 ± 0.97 μmol/L, p = .001), ALT (42.86 ± 11.15 compared with 40.60 ± 9.89 U/L, p = .018), and AST (49.45 ± 12.39 compared with 46.30 ± 10.85 U/L, p = .002) at the end of the study. Based on analysis of covariance, a significant decrease was also observed in levels of NTBI (2.22 ± 0.97 vs. 2.55 ± 0.94 μmol/L, p = .026), ALT (40.60 ± 9.89 vs. 45.01 ± 10.42 U/L, p = .004), and AST (46.30 ± 10.85 vs. 50.99 ± 9.36 U/L, p = .009) in curcumin group in comparison with placebo group. There were no significant changes in hepcidin and other variables in any of the 2 groups. Curcumin administration alleviated iron burden and liver dysfunction by reducing NTBI, ALT, and AST levels in patients with β-thalassemia major.
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Affiliation(s)
- Elahe Mohammadi
- National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Tamaddoni
- Pediatric Hematology and Oncology, Non-Communicable Pediatric Diseases Research Center, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Durdi Qujeq
- Clinical Biochemistry, Cellular and Molecular Biology Research Center, Health Research Institute, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Esmat Nasseri
- Nutritional Sciences, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farid Zayeri
- Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Zand
- Biochemistry, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Gholami
- Clinical Biochemistry, Faculty of medicine, Babol University of Medical sciences, Babol, Iran
| | - Seyed Mostafa Mir
- Clinical Biochemistry, Faculty of medicine, Babol University of Medical sciences, Babol, Iran
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Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients. Expert Rev Hematol 2018; 11:471-479. [DOI: 10.1080/17474086.2018.1476134] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Natthaphat Siri-Angkul
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
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17
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Nasseri E, Mohammadi E, Tamaddoni A, Qujeq D, Zayeri F, Zand H. Benefits of Curcumin Supplementation on Antioxidant Status in β-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial. ANNALS OF NUTRITION AND METABOLISM 2017; 71:136-144. [DOI: 10.1159/000479634] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/19/2017] [Indexed: 01/11/2023]
Abstract
Background: β-Thalassemia major, the most common inherited anemia in the world, is associated with imbalance in the oxidant-antioxidant system. The objective of this study was to evaluate the efficacy of curcumin supplementation on markers of oxidative stress in patients with β-Thalassemia. Methods: This double-blind randomized controlled clinical trial was performed on 61 β-thalassemia major patients. Subjects in the curcumin group received two 500 mg curcumin capsules daily and patients in the placebo group took 2 placebo capsules daily for 12 weeks. Dietary intakes and biochemical parameters were assessed at the beginning and the end of intervention. Results: At the end of the study, serum malondialdehyde (MDA), total and direct bilirubin significantly decreased (p = 0.002, p < 0.001, and p < 0.001, respectively) and total antioxidant capacity significantly increased (p = 0.005) in the curcumin group. Based on the analysis of covariance, a significant reduction in MDA, total and direct bilirubin was also detected in the curcumin group when compared to the placebo group (p = 0.001, p = 0.039, and p = 0.013, respectively). Changes in hemoglobin, serum iron, ferritin, catalase, and vitamin E were not significant in any of the 2 groups. Conclusions: Curcumin supplementation in combination with deferoxamin improved the antioxidant status in β-thalassemia major patients. Curcumin may be useful for the relief of metabolic complications in these patients.
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Kumfu S, Fucharoen S, Chattipakorn SC, Chattipakorn N. Cardiac complications in beta-thalassemia: From mice to men. Exp Biol Med (Maywood) 2017; 242:1126-1135. [PMID: 28485683 DOI: 10.1177/1535370217708977] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future. Impact statement Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of iron overload on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed.
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Affiliation(s)
- Sirinart Kumfu
- 1 Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai 50200, Thailand.,2 Faculty of Medicine, Department of Physiology, Cardiac Electrophysiology Unit, Chiang Mai University, Chiang Mai 50200, Thailand.,3 Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Suthat Fucharoen
- 4 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Siriporn C Chattipakorn
- 1 Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai 50200, Thailand.,3 Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.,5 Faculty of Dentistry, Department of Oral Biology and Diagnostic Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nipon Chattipakorn
- 1 Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai 50200, Thailand.,2 Faculty of Medicine, Department of Physiology, Cardiac Electrophysiology Unit, Chiang Mai University, Chiang Mai 50200, Thailand.,3 Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand
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19
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Sangartit W, Pakdeechote P, Kukongviriyapan V, Donpunha W, Shibahara S, Kukongviriyapan U. Tetrahydrocurcumin in combination with deferiprone attenuates hypertension, vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron-overloaded mice. Vascul Pharmacol 2016; 87:199-208. [PMID: 27713040 DOI: 10.1016/j.vph.2016.10.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 10/01/2016] [Accepted: 10/01/2016] [Indexed: 12/13/2022]
Abstract
Excessive iron can generate reactive oxygen species (ROS), leading to oxidative stress that is closely associated with cardiovascular dysfunction. Iron overload was induced in male ICR mice by injection of iron sucrose (10mg/kg/day) for eight weeks. Iron overload was evidenced by increased serum iron indices. The mice developed increased blood pressure, impaired vascular function and blunted response of the autonomic nervous system. These effects were accompanied by increased malondialdehyde levels in various tissues, increased nitric oxide metabolites in plasma and urine, and decreased blood glutathione. Tetrahydrocurcumin (THU, 50mg/kg/day), deferiprone (or L1, 50mg/kg/day) or both was orally administered throughout the period of iron sucrose injection. The treatments significantly alleviated the deleterious cardiovascular effects of iron overload, and were associated with modulation of nitric oxide levels. An imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in response to iron overload was normalized by THU, L1 or the combination treatment. Moreover, the treatment decreased the upregulated expression levels of gp91phox, p47phox and HO-1. The combination of THU and L1 exerted a greater effect than THU or L1 monotherapy. These results suggest beneficial effects of THU and L1 on iron-induced oxidative stress, hypertension, and vascular dysfunction.
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Affiliation(s)
- Weerapon Sangartit
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Poungrat Pakdeechote
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Veerapol Kukongviriyapan
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Wanida Donpunha
- Department of Physical Therapy, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Shigeki Shibahara
- Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan
| | - Upa Kukongviriyapan
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
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20
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Samniang B, Shinlapawittayatorn K, Chunchai T, Pongkan W, Kumfu S, Chattipakorn SC, KenKnight BH, Chattipakorn N. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats. Sci Rep 2016; 6:19749. [PMID: 26830020 PMCID: PMC4735283 DOI: 10.1038/srep19749] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 12/17/2015] [Indexed: 01/02/2023] Open
Abstract
Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats.
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Affiliation(s)
- Bencharunan Samniang
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Krekwit Shinlapawittayatorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Titikorn Chunchai
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Wanpitak Pongkan
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Sirinart Kumfu
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Siriporn C. Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand
| | | | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
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21
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Wongjaikam S, Kumfu S, Chattipakorn SC, Fucharoen S, Chattipakorn N. Current and future treatment strategies for iron overload cardiomyopathy. Eur J Pharmacol 2015; 765:86-93. [DOI: 10.1016/j.ejphar.2015.08.017] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 08/11/2015] [Accepted: 08/12/2015] [Indexed: 02/01/2023]
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Koonrungsesomboon N, Tantiworawit A, Phrommintikul A, Saekho S, Srichairattanakool S, Chattipakorn N. Heart Rate Variability for Early Detection of Iron Overload Cardiomyopathy in β-Thalassemia Patients. Hemoglobin 2015; 39:281-6. [PMID: 26029793 DOI: 10.3109/03630269.2015.1043059] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Iron overload cardiomyopathy remains the major cause of death in β-thalassemia (β-thal). Conventional routine screening parameters such as serum ferritin and echocardiogram (ECG) do not permit early detection of this condition. Although non-transferrin-bound iron (NTBI) is a reliable indicator for iron overload, it is still not universally available. Recently, heart rate variability (HRV), representing cardiac autonomic function, was found to be depressed in thalassemia patients. We hypothesized that HRV can be used for early detection of iron overload cardiomyopathy. Fifty patients (aged 29 ± 11 years; 31 females and 19 males) with β-thal were enrolled. The 24-hour Holter monitoring for HRV, serum ferritin, NTBI, hematological values and ECG were performed for each patient. Of the 50 patients, 29 carried β-thal major (β-TM). Non-transferrin-bound iron was weakly correlated to all time-domain HRV parameters. Low- and high-frequency domain HRV parameters were also inversely weakly correlated with NTBI. Neither HRV nor NTBI was correlated with serum ferritin. With its weak but significant correlation with NTBI, HRV may be considered to be used as a potential indicator of an iron overload condition and an early marker of cardiac involvement in patients with β-thal.
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Affiliation(s)
- Nut Koonrungsesomboon
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University , Chiang Mai , Thailand
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23
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Chansiw N, Pangjit K, Phisalaphong C, Porter JB, Evans P, Fucharoen S, Srichairatanakool S. Effect of a novel oral active iron chelator: 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in iron-overloaded and non-overloaded mice. ASIAN PAC J TROP MED 2014; 7S1:S155-61. [PMID: 25312112 DOI: 10.1016/s1995-7645(14)60223-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Revised: 04/10/2014] [Accepted: 05/13/2014] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To evaluate efficacy and toxicity of a novel orally active bidentate iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in mice under normal and iron overload conditions. METHODS Wild type C57BL/6 mice were fed with normal and 0.2% (w/w) ferrocene-supplemented (Fe) diets, respectively for 240 d and orally given the CM1 (50, 100 and 200 mg/kg) for 180 d. Blood iron profiles, hematological indices, liver enzymes and histopathology were determined. RESULTS CM1 treatment lowered plasma levels of labile plasma iron and non-transferrin bound iron, but not ferritin in the Fe-fed mice. However, the treatment did not impact blood hemoglobin level, white blood cell and platelet numbers in both normal diet and Fe diet-fed mice. Interestingly, CM1 treatment did not markedly elevate plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in the normal diet-fed mice but it tended to increase the levels of the liver enzymes slightly in the Fe-fed mice. Hematoxylin and eosin staining result showed no abnormal pathological changes in heart, liver and spleen tissues. CONCLUSIONS It is clear that CM1 would not be toxic to bone marrow and liver cells under normal and iron-overload conditions.
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Affiliation(s)
- Nittaya Chansiw
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Kanjana Pangjit
- College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand
| | - Chada Phisalaphong
- Institute of Research and Development, Government Pharmaceutical Organization, Ministry of Public Health, Bangkok 10400, Thailand
| | - John B Porter
- Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, 86, Huntley Street, London, WC1E 6BT, United Kingdom
| | - Patricia Evans
- Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, 86, Huntley Street, London, WC1E 6BT, United Kingdom
| | - Suthat Fucharoen
- Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University Salaya Campus, Nakornpathom 73170, Thailand
| | - Somdet Srichairatanakool
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
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Kulprachakarn K, Chansiw N, Pangjit K, Phisalaphong C, Fucharoen S, Hider RC, Santitherakul S, Srichairatanakool S. Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loading β-thalassemic mice. Asian Pac J Trop Biomed 2014; 4:663-8. [PMID: 25183338 DOI: 10.12980/apjtb.4.2014apjtb-2014-0155] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 07/12/2014] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVE To evaluate the iron-chelating properties and free-radical scavenging activities of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) treatment in chronic iron-loaded β-thalassemic (BKO) mice. METHODS The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1 [50 mg/(kg.day)] for 6 months. Blood levels of non-transferrin bound iron, labile plasma iron, ferritin (Ft) and malondialdehyde were determined. RESULTS The BKO mice were fed with an iron diet for 8 months which resulted in iron overload. Interestingly, the mice showed a decrease in the non-transferrin bound iron, labile plasma iron and malondialdehyde levels, but not the Ft levels after continuous CM1 treatment. CONCLUSIONS CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β-thalassemic mice.
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Affiliation(s)
- Kanokwan Kulprachakarn
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nittaya Chansiw
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Kanjana Pangjit
- College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, Thailand
| | - Chada Phisalaphong
- Institute of Research and Development, Government Pharmaceuticals Organization, Ministry of Public Health, Thailand
| | - Suthat Fucharoen
- Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University Salaya Campus, Nakornprathom, Thailand
| | - Robert C Hider
- Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, London, United Kingdom
| | - Sineenart Santitherakul
- Medical Science Research Equipment Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats. Eur J Nutr 2013; 53:919-28. [PMID: 24142245 DOI: 10.1007/s00394-013-0595-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 10/03/2013] [Indexed: 01/14/2023]
Abstract
PURPOSE Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. METHODS Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. RESULTS Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. CONCLUSION We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.
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Koonrungsesomboon N, Chattipakorn SC, Fucharoen S, Chattipakorn N. Early detection of cardiac involvement in thalassemia: From bench to bedside perspective. World J Cardiol 2013; 5:270-279. [PMID: 24009816 PMCID: PMC3761180 DOI: 10.4330/wjc.v5.i8.270] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 07/31/2013] [Accepted: 08/06/2013] [Indexed: 02/06/2023] Open
Abstract
Myocardial siderosis is known as the major cause of death in thalassemia major (TM) patients since it can lead to iron overload cardiomyopathy. Although this condition can be prevented if timely effective intensive chelation is given to patients, the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition. Various direct and indirect methods of iron assessment, including serum ferritin level, echocardiogram, non-transferrin-bound iron, cardiac magnetic resonance T2*, heart rate variability, and liver biopsy and myocardial biopsy, have been proposed for early detection of cardiac iron overload in TM patients. However, controversial evidence and limitations of their use in clinical practice exist. In this review article, all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented. Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients, these two methods are also presented and discussed. The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.
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Moayedi B, Gharagozloo M, Esmaeil N, Maracy MR, Hoorfar H, Jalaeikar M. A randomized double-blind, placebo-controlled study of therapeutic effects of silymarin in β-thalassemia major patients receiving desferrioxamine. Eur J Haematol 2013; 90:202-9. [PMID: 23278124 DOI: 10.1111/ejh.12061] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2012] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Thalassemia is one of the most common genetic disorders worldwide. Chronic blood transfusions treat the underlying anemia but may lead to iron toxicity. Effective iron chelation remains one of the main targets of clinical management of thalassemia major. In this study, iron-chelating activity of silymarin, a flavonolignan isolated from silybum marianum, was examined in β-thalassemia major. METHODS Patients were treated with the combination of desferrioxamine and silymarin (Legalon(®) ; n = 49) or desferrioxamine plus placebo (n = 48) for 9 months. The serum levels of ferritin, iron, total iron-binding capacity (TIBC), soluble transferrin receptor, and hepcidin were determined at the baseline and after 9-month therapy. Liver function test was performed before and after treatment in both groups. RESULTS Serum ferritin levels decreased significantly from the beginning to the end of silymarin treatment (3028.8 ± 2002.6 vs. 1972.2 ± 1250.6 ng/mL); however, no significant change in serum ferritin was observed in the patients receiving placebo (2249.0 ± 1304.2 vs. 2015.6 ± 1146.8). Moreover, serum iron and TIBC levels were significantly reduced in silymarin group compared with placebo. Patients on silymarin therapy also exhibited a significant decrease in serum levels of hepcidin and soluble transferrin receptor after 9-month treatment period. A significant improvement in liver function test was observed in silymarin group in comparison with placebo. CONCLUSION This study shows that silymarin is effective at reducing iron overload in patients when used in conjunction with desferrioxamine. Therapeutic effects of silymarin on a background of desferrioxamine suggest the potential effectiveness of silymarin alone in reducing body iron burden.
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Affiliation(s)
- Behjat Moayedi
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Role of curcuminoids in ameliorating oxidative modification in β-thalassemia/Hb E plasma proteome. J Nutr Biochem 2013; 24:578-85. [DOI: 10.1016/j.jnutbio.2012.02.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2011] [Revised: 02/08/2012] [Accepted: 02/14/2012] [Indexed: 02/02/2023]
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Abstract
Abstract
Sickle cell disease and thalassemia have distinctly different mutations, but both share common complications from a chronic vasculopathy. In the past, fetal hemoglobin–modulating drugs have been the main focus of new therapy, but the increased understanding of the complex pathophysiology of these diseases has led to the development of novel agents targeting multiple pathways that cause vascular injury. This review explores the pathophysiology of hemoglobinopathies and novel drugs that have reached phase 1 and 2 clinical trials. Therapies that alter cellular adhesion to endothelium, inflammation, nitric oxide dysregulation, oxidative injury, altered iron metabolism, and hematopoiesis will be highlighted. To evaluate these therapies optimally, recommendations for improving clinical trial design in hemoglobinopathies are discussed.
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Apaijai N, Pintana H, Chattipakorn SC, Chattipakorn N. Cardioprotective effects of metformin and vildagliptin in adult rats with insulin resistance induced by a high-fat diet. Endocrinology 2012; 153:3878-85. [PMID: 22621958 DOI: 10.1210/en.2012-1262] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction. Whereas metformin is a widely used antidiabetic drug to improve insulin resistance, vildagliptin is a novel oral antidiabetic drug in a group of dipeptidyl peptidase-4 inhibitors in which its cardiac effect is unclear. This study aimed to determine the cardiovascular effects of metformin and vildagliptin in rats with insulin resistance induced by high-fat diet. Male Wistar rats were fed with either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group were divided into three subgroups to receive the vehicle, metformin (30 mg/kg, twice daily), or vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined and compared among these treatment groups. Rats exposed to a high-fat diet developed increased body weight, visceral fat, plasma insulin, cholesterol, oxidative stress, depressed HRV, and cardiac mitochondrial dysfunction. Metformin and vildagliptin did not alter body weight and plasma glucose levels but decreased the plasma insulin, total cholesterol, and oxidative stress levels. Although both metformin and vildagliptin attenuated the depressed HRV, cardiac dysfunction, and cardiac mitochondrial dysfunction, vildagliptin was more effective in this prevention. Furthermore, only vildagliptin prevented cardiac mitochondrial membrane depolarization caused by consumption of a high-fat diet. We concluded that vildagliptin is more effective in preventing cardiac sympathovagal imbalance and cardiac dysfunction, as well as cardiac mitochondrial dysfunction, than metformin in rats with insulin resistance induced by high-fat diet.
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Affiliation(s)
- Nattayaporn Apaijai
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
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