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Czlapka-Matyasik M, Wadolowska L, Gut P, Gramza-Michałowska A. Changes in Oxidative Stress, Inflammatory Markers, and Lipid Profile After a 6-Week High-Antioxidant-Capacity Dietary Intervention in CVD Patients. Nutrients 2025; 17:806. [PMID: 40077675 PMCID: PMC11902212 DOI: 10.3390/nu17050806] [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: 12/31/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: Increased dietary antioxidant capacity is a good means of lowering oxidative stress and cardiovascular risk. Established antioxidant capacity doses should be tested using dietary intervention. Methods: We analysed the influence of a high-antioxidant-capacity diet on oxidative stress (OS) and inflammatory and lipid profile in CVD (cardiovascular disease) subjects with initially low (LowA) and high (HighA) antioxidant capacity markers. It was an experimental study with a 6-week dietary intervention (DI). Forty-eight CVD patients completed the DI. Blood and urine samples were collected, and anthropometric measurements were taken. Dietary data were collected using a multi-day food record method. α-tocopherol, β-carotene, and retinol were chosen as antioxidant capacity markers; F2-isoprostanes (F2-IsoP), oxidised low-density lipoproteins (oxLDL), and uric acid (UA) were used as OS markers; and interleukin 6 (IL-6) and high-sensitivity C-reactive proteins (hs-CRP) were used as inflammatory markers. Total cholesterol, low- and high-density lipoproteins, and triglycerides (TCHOL, LDL, HDL, TRI) as lipid profiles were analysed. Two groups of subjects with LowA and HighA profiles were identified. Results: The total dietary antioxidant capacity intake during DI was increased by 56%. In the total sample, the DI increased β-carotene, retinol, and UA, and decreased IL-6 oxLDL. The LowA group exhibited increased β-carotene, α-tocopherol, retinol, and decreased IL-6. The HighA group exhibited increased β-carotene and decreased IL-6, F2-IsoP, oxLDL, and oxLDL/LDL ratio. In the HighA group, compared to the LowA group, greater decreases in α-tocopherol and F2-IsoP were found. In both groups, inflammatory markers (IL-6) decreased, and β-carotene increased. Conclusions: The DI results depended on the antioxidant capacity profile at baseline; nevertheless, the established DI including selected antioxidative snacks significantly decrease oxidative stress and improve antioxidant capacity. Further research on diet natural antioxidant supplementation needs to be continued.
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Affiliation(s)
| | - Lidia Wadolowska
- Department of Human Nutrition, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland;
| | - Paweł Gut
- Department of Endocrinology, Metabolism, and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland;
| | - Anna Gramza-Michałowska
- Department of Gastronomy Sciences and Functional Foods, Poznan University of Life Sciences, 60-624 Poznan, Poland;
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Du K, Liu Y, Zhao X, Wang H, Wan X, Sun X, Luo W. Global research trends and hotspots of oxidative stress in diabetic retinopathy (2000-2024). Front Endocrinol (Lausanne) 2024; 15:1428411. [PMID: 39220368 PMCID: PMC11361963 DOI: 10.3389/fendo.2024.1428411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024] Open
Abstract
Introduction Oxidative stress has been identified as a major contributor to the pathogenesis of DR, and many diagnostic and therapeutic strategies have been developed to target oxidative stress. Our aim was to understand the contribution of the country of origin of the publication, the institution, the authors, and the collaborative relationship between them. Methods We performed a bibliometric analysis to summarize and explore the research hotspots and trends of oxidative stress in the DR. Results We observe an upward trend in the number of posts on related topics from year to year. Expanding on this, Queens University Belfast is the most influential research institution. Current research hotspots and trends focus on the mechanism of autophagy and NLRP3 inflammasome's role in oxidative stress in DR. Discussion We conducted a multi-dimensional analysis of the research status of oxidative stress in diabetic retinopathy through bibliometric analysis, and proposed possible future research trends and hotspots.
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Affiliation(s)
| | | | | | | | | | | | - Wenjuan Luo
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Garcia BREV, Makiyama EN, Sampaio GR, Soares-Freitas RAM, Bonvini A, Amaral AG, Bordin S, Fock RA, Rogero MM. Effects of Branched-Chain Amino Acids on the Inflammatory Response Induced by LPS in Caco-2 Cells. Metabolites 2024; 14:76. [PMID: 38276311 PMCID: PMC10821323 DOI: 10.3390/metabo14010076] [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: 12/15/2023] [Revised: 01/09/2024] [Accepted: 01/20/2024] [Indexed: 01/27/2024] Open
Abstract
Branched-chain amino acids (BCAA) are essential for maintaining intestinal mucosal integrity. However, only a few studies have explored the role of BCAA in the modulation of intestinal inflammation. In this study, we investigated in vitro effects of BCAA on the inflammatory response induced by lipopolysaccharide (LPS) (1 µg/mL) in Caco-2 cells. Caco-2 cells were assigned to six groups: control without BCAA (CTL0), normal BCAA (CTL; 0.8 mM leucine, 0.8 mM isoleucine, and 0.8 mM valine); leucine (LEU; 2 mM leucine), isoleucine (ISO; 2 mM isoleucine), valine (VAL; 2 mM valine), and high BCAA (LIV; 2 mM leucine, 2 mM isoleucine, and 2 mM valine). BCAA was added to the culture medium 24 h before LPS stimulation. Our results indicated that BCAA supplementation did not impair cell viability. The amino acids leucine and isoleucine attenuated the synthesis of IL-8 and JNK and NF-kB phosphorylation induced by LPS. Furthermore, neither BCAA supplementation nor LPS treatment modulated the activity of glutathione peroxidase or the intracellular reduced glutathione/oxidized glutathione ratio. Therefore, leucine and isoleucine exert anti-inflammatory effects in Caco-2 cells exposed to LPS by modulating JNK and NF-kB phosphorylation and IL-8 production. Further in vivo studies are required to validate these findings and gather valuable information for potential therapeutic or dietary interventions.
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Affiliation(s)
- Bruna Ruschel Ewald Vega Garcia
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo 01246-904, Brazil; (B.R.E.V.G.); (G.R.S.); (R.A.M.S.-F.)
| | - Edson Naoto Makiyama
- Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (E.N.M.); (R.A.F.)
| | - Geni Rodrigues Sampaio
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo 01246-904, Brazil; (B.R.E.V.G.); (G.R.S.); (R.A.M.S.-F.)
| | | | - Andrea Bonvini
- Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of Sao Paulo, São Paulo 05508-000, Brazil;
| | - Andressa Godoy Amaral
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo 05508-000, Brazil; (A.G.A.); (S.B.)
| | - Silvana Bordin
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo 05508-000, Brazil; (A.G.A.); (S.B.)
| | - Ricardo Ambrósio Fock
- Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil; (E.N.M.); (R.A.F.)
| | - Marcelo Macedo Rogero
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo 01246-904, Brazil; (B.R.E.V.G.); (G.R.S.); (R.A.M.S.-F.)
- Food Research Center (FoRC), CEPID-FAPESP (Research Innovation and Dissemination Centers São Paulo Research Foundation), São Paulo 05508-000, Brazil
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Chi T, Sang T, Wang Y, Ye Z. Cleavage and Noncleavage Chemistry in Reactive Oxygen Species (ROS)-Responsive Materials for Smart Drug Delivery. Bioconjug Chem 2024; 35:1-21. [PMID: 38118277 DOI: 10.1021/acs.bioconjchem.3c00476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2023]
Abstract
The design and development of advanced drug delivery systems targeting reactive oxygen species (ROS) have gained significant interest in recent years for treating various diseases, including cancer, psychiatric diseases, cardiovascular diseases, neurological diseases, metabolic diseases, and chronic inflammations. Integrating specific chemical bonds capable of effectively responding to ROS and triggering drug release into the delivery system is crucial. In this Review, we discuss commonly used conjugation linkers (chemical bonds) and categorize them into two groups: cleavable linkers and noncleavable linkers. Our goal is to clarify their unique drug release mechanisms from a chemical perspective and provide practical organic synthesis approaches for their efficient production. We showcase numerous significant examples to demonstrate their synthesis routes and diverse applications. Ultimately, we strive to present a comprehensive overview of cleavage and noncleavage chemistry, offering insights into the development of smart drug delivery systems that respond to ROS.
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Affiliation(s)
- Teng Chi
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States
| | - Ting Sang
- School of Stomatology of Nanchang University & Jiangxi Province Clinical Research Center for Oral Diseases & The Key Laboratory of Oral Biomedicine, Nanchang 330006, China
| | - Yanjing Wang
- Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States
| | - Zhou Ye
- Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong S.A.R. 999077, China
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Lee E, Park HY, Kim SW, Sun Y, Choi JH, Seo J, Jung YP, Kim AJ, Kim J, Lim K. Enhancing Supplemental Effects of Acute Natural Antioxidant Derived from Yeast Fermentation and Vitamin C on Sports Performance in Triathlon Athletes: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial. Nutrients 2023; 15:3324. [PMID: 37571262 PMCID: PMC10421245 DOI: 10.3390/nu15153324] [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: 06/19/2023] [Revised: 07/23/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
This study investigated the acute effects of natural antioxidants, derived from yeast fermentation containing glutathione and dietary vitamin C supplementation, on metabolic function, skeletal muscle oxygenation, cardiac function, and antioxidant function during submaximal exercise in middle-aged triathlon athletes. Twelve participants (aged 49.42 ± 5.9 years) completed 90 min submaximal cycling trials corresponding to 70% maximal oxygen uptake with either vitamin C and glutathione (VitC+Glu), vitamin C (VitC), glutathione (Glu) supplementation, or placebo. Metabolic function (minute ventilation, oxygen uptake, carbon dioxide output [VCO2], respiratory exchange ratio [RER], oxygen pulse [O2pulse], carbohydrate oxidation, fat oxidation, and energy expenditure), skeletal muscle oxygenation (oxidized hemoglobin and myoglobin in skeletal muscle tissue, total hemoglobin and myoglobin in skeletal muscle tissue [tHb]), cardiac function (heart rate [HR], stroke volume [SV], cardiac output, end-diastolic volume, end-systolic volume, and ejection fraction), and antioxidant function parameters (blood lactate, superoxide dismutase, catalase, glutathione peroxidases, glutathione [GSH], diacron reactive oxygen metabolite [dROM], and biological antioxidant potential [BAP]) were measured during submaximal exercise and recovery. VCO2, RER, HR, blood lactate after exercise, and dROM were significantly lower, and O2pulse, tHb, and BAP were significantly higher for VitC+Glu than for the other trials (p < 0.05). In conclusion, combined vitamin C and glutathione supplementation was more effective in improving metabolic function, skeletal oxygenation, cardiac function, and antioxidant function during prolonged submaximal exercise in middle-aged triathletes.
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Affiliation(s)
- Eunjoo Lee
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
| | - Hun-Young Park
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
- Physical Activity and Performance Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Sung-Woo Kim
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
- Physical Activity and Performance Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Yerin Sun
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
| | - Jae-Ho Choi
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
| | - Jisoo Seo
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
| | - Yanghoon Peter Jung
- CJ CheilJedang Food & Nutrition Tech, Jung-gu, Seoul 04527, Republic of Korea; (Y.P.J.); (A.-J.K.)
| | - Ah-Jin Kim
- CJ CheilJedang Food & Nutrition Tech, Jung-gu, Seoul 04527, Republic of Korea; (Y.P.J.); (A.-J.K.)
| | - Jisu Kim
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
- Physical Activity and Performance Institute, Konkuk University, Seoul 05029, Republic of Korea
| | - Kiwon Lim
- Department of Sports Medicine and Science, Graduate School, Konkuk University, Seoul 05029, Republic of Korea; (E.L.); (H.-Y.P.); (S.-W.K.); (Y.S.); (J.-H.C.); (J.S.); (J.K.)
- Physical Activity and Performance Institute, Konkuk University, Seoul 05029, Republic of Korea
- Department of Physical Education, Konkuk University, Seoul 05029, Republic of Korea
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Osman AG, Avula B, Katragunta K, Ali Z, Chittiboyina AG, Khan IA. Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders. Molecules 2023; 28:molecules28073148. [PMID: 37049909 PMCID: PMC10096080 DOI: 10.3390/molecules28073148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/24/2023] [Accepted: 03/29/2023] [Indexed: 04/05/2023] Open
Abstract
Elderberry is highly reputed for its health-improving effects. Multiple pieces of evidence indicate that the consumption of berries is linked to enhancing human health and preventing or delaying the onset of chronic medical conditions. Compared with other fruit, elderberry is a very rich source of anthocyanins (approximately 80% of the polyphenol content). These polyphenols are the principals that essentially contribute to the high antioxidant and anti-inflammatory capacities and the health benefits of elderberry fruit extract. These health effects include attenuation of cardiovascular, neurodegenerative, and inflammatory disorders, as well as anti-diabetic, anticancer, antiviral, and immuno-stimulatory effects. Sales of elderberry supplements skyrocketed to $320 million over the year 2020, according to an American Botanical Council (ABC) report, which is attributable to the purported immune-enhancing effects of elderberry. In the current review, the chemical composition of the polyphenolic content of the European elderberry (Sambucus nigra) and the American elderberry (Sambucus canadensis), as well as the analytical techniques employed to analyze, characterize, and ascertain the chemical consistency will be addressed. Further, the factors that influence the consistency of the polyphenolic chemical composition, and hence, the consistency of the health benefits of elderberry extracts will be presented. Additionally, adulteration and safety as factors contributing to consistency will be covered. The role of elderberry in enhancing human health alone with the pharmacological basis, the cellular pathways, and the molecular mechanisms underlying the observed health benefits of elderberry fruit extracts will be also reviewed.
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Affiliation(s)
- Ahmed G. Osman
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
| | - Bharathi Avula
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
| | - Kumar Katragunta
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
| | - Zulfiqar Ali
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
| | - Amar G. Chittiboyina
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
| | - Ikhlas A. Khan
- National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
- Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA
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Effect of Berberine on the Status of Antioxidants in the Heart of Lead-Exposed Rats. Pharm Chem J 2023. [DOI: 10.1007/s11094-023-02837-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2023]
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Varela ELP, Gomes ARQ, da Silva Barbosa dos Santos A, de Carvalho EP, Vale VV, Percário S. Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases. Nutrients 2022; 14:5303. [PMID: 36558462 PMCID: PMC9787606 DOI: 10.3390/nu14245303] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/10/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. This review aimed to describe the main mechanisms inducing oxidative stress during malaria, highlighting the production of RONS as a defense mechanism against the infection induced by the ischemia-reperfusion syndrome, the metabolism of the parasite, and the metabolism of antimalarial drugs. Furthermore, the effects of lycopene on several diseases in which oxidative stress is implicated as a cause are outlined, providing information about its mechanism of action, and providing an evidence-based justification for its supplementation in malaria.
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Affiliation(s)
- Everton Luiz Pompeu Varela
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil
- Post-Graduate Program in Biodiversity and Biotechnology of the BIONORTE Network, Federal University of Pará, Belém 66075-110, Brazil
| | - Antônio Rafael Quadros Gomes
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil
- Post-Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém 66075-110, Brazil
| | - Aline da Silva Barbosa dos Santos
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil
- Post-Graduate Program in Biodiversity and Biotechnology of the BIONORTE Network, Federal University of Pará, Belém 66075-110, Brazil
| | - Eliete Pereira de Carvalho
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil
- Post-Graduate Program in Biodiversity and Biotechnology of the BIONORTE Network, Federal University of Pará, Belém 66075-110, Brazil
| | - Valdicley Vieira Vale
- Post-Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém 66075-110, Brazil
| | - Sandro Percário
- Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil
- Post-Graduate Program in Biodiversity and Biotechnology of the BIONORTE Network, Federal University of Pará, Belém 66075-110, Brazil
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Wang L, Yi Z. Association of the Composite dietary antioxidant index with all-cause and cardiovascular mortality: A prospective cohort study. Front Cardiovasc Med 2022; 9:993930. [PMID: 36267633 PMCID: PMC9577254 DOI: 10.3389/fcvm.2022.993930] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/16/2022] [Indexed: 12/05/2022] Open
Abstract
Background According to epidemiological and experimental data, high individual dietary antioxidant intake is correlated with reduced cancer risk. The correlations between combined dietary antioxidants and the risk of all-cause and cardiovascular mortality remain unclear. Consequently, this study focused on evaluating the correlation between the food-derived Composite Dietary Antioxidant Index (CDAI) and all-cause and cardiovascular mortality. Materials and methods Two years of data collected from participants aged ≥20 years were included in this prospective cohort study, which was obtained from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The US NHANES adopted a complicated, multistage probability sampling method to collect health data representing the US population. Data collection was done through in-person interviews, virtual physical examinations, and laboratory tests. Mortality-related follow-up statistics from the start of the survey to 31 December 2019 were available. The shape of the correlation between CDAI and all-cause and cardiovascular mortality was inspected using a restricted cubic spline model. For CDAI and all-cause and cardiovascular mortality, the univariate- and multivariate-adjusted Cox proportional hazard models were estimated and presented as regression coefficients and 95% confidence intervals. Results In total, 44,031 NHANES participants represented 339.4 million non-institutionalized residents of the US (age, 47.2 ± 16.9 years; 52.5% women, 70.2% non-Hispanic whites, 10.8% non-Hispanic black people, and 7.5% Mexican Americans). In the 118-month follow-up, 9,249 deaths were reported, including 2,406 deaths resulting from heart disease and 519 deaths due to cerebrovascular disease. In the restricted cubic spline regression models, a linear relationship between CDAI and all-cause mortality was present. The weighted multivariate hazard ratios for all-cause mortality were computed to be 0.97 (0.87–1.07) for Q2, 0.88 (0.81–0.96) for Q3, and 0.90 (0.80–1.00) for Q4 (P for trend = 0.009) upon comparison with the lowest quartile of CDAI, and an identical trend was observed for cardiovascular mortality. Conclusion A high CDAI was linked to decreased all-cause and cardiovascular mortality risk. The intake of an antioxidant-rich diet significantly prevents cardiovascular mortality. To shed more light on these outcomes, more itemized investigations such as randomized control trials are required.
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Affiliation(s)
- Lei Wang
- Department of Cardiology, Aerospace Center Hospital, Beijing, China
| | - Zhong Yi
- Department of Geriatric Medicine, Aerospace Center Hospital, Beijing, China,*Correspondence: Zhong Yi,
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Rahmatullah M, Jahan R, Nissapatorn V, Pereira MDL, Wiart C. Editorial: Emerging and old viral diseases: Antiviral drug discovery from medicinal plants. Front Pharmacol 2022; 13:976592. [PMID: 36059941 PMCID: PMC9437638 DOI: 10.3389/fphar.2022.976592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Mohammed Rahmatullah
- Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, University of Development Alternative, Dhaka, Bangladesh
- *Correspondence: Mohammed Rahmatullah,
| | - Rownak Jahan
- Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, University of Development Alternative, Dhaka, Bangladesh
| | - Veeranoot Nissapatorn
- School of Allied Health Sciences and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat, Thailand
| | - Maria De Lourdes Pereira
- CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Christophe Wiart
- School of Pharmacy, University of Nottingham Malaysia Campus, Selangor, Malaysia
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Khodarahmi M, Sobhrakhshan Khah A, Farhangi MA, Siri G, Kahroba H. Dietary total antioxidant capacity interacts with a variant of chromosome 5q13-14 locus to influence cardio-metabolic risk factors among obese adults. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022; 23:117. [PMID: 37521830 PMCID: PMC9362403 DOI: 10.1186/s43042-022-00328-3] [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] [Received: 08/31/2021] [Accepted: 07/28/2022] [Indexed: 11/24/2022] Open
Abstract
Background The association between cocaine- and amphetamine-regulated transcript prepropeptide gene (CARTPT) and obesity-related outcomes has shown in the epidemiological studies. Nevertheless, there is lack of data regarding the CARTPT gene-diet interactions in terms of antioxidant potential of diet. So, this study aimed to test CARTPT gene-dietary non-enzymatic antioxidant capacity (NEAC) interactions on cardio-metabolic risk factors in obese individuals. Methods and material The present cross-sectional study was carried out among 288 apparently healthy obese adults within age range of 20-50 years. Antioxidant capacity of diet was estimated by calculating the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC) using a semiquantitative food frequency questionnaire (FFQ). Genotyping for CARTPT rs2239670 polymorphism was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results A significant interaction was revealed between CARTPT rs2239670 and dietary ORAC on BMI (PInteraction = 0.048) and fat mass percent (FM%) (PInteraction = 0.008); in A allele carriers, higher adherence to the dietary ORAC was related to lower level of BMI and FM%. And, the significant interactions were observed between FRAP index and rs2239670 in relation to HOMA (PInteraction = 0.049) and QUICKI (PInteraction = 0.048). Moreover, there were significant interactions of rs2239670 with TRAP (PInteraction = 0.029) and TEAC (PInteraction = 0.034) on the serum glucose level; individuals with AG genotype were more respondent to higher intake of TRAP. Conclusion The present study indicated that the relationships between CARTPT rs2239670 and obesity and its-related metabolic parameters depend on adherence to the dietary NEAC. Large prospective studies are needed to confirm our findings.
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Affiliation(s)
- Mahdieh Khodarahmi
- Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Sobhrakhshan Khah
- Sepehr Heart Center, Baharloo Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdieh Abbasalizad Farhangi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Attar-neishabouri Ave, Golgasht St, Tabriz, 5165665931 Iran
| | - Goli Siri
- Department of Internal Medicine, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Houman Kahroba
- Department of Toxicogenomics, GROW School of Oncology and Development Biology, Maastricht University, Maastricht, The Netherlands
- Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium
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12
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Haridevamuthu B, Manjunathan T, Guru A, Kumar RS, Rajagopal R, Kuppusamy P, Juliet A, Gopinath P, Arockiaraj J. Hydroxyl containing benzo[b]thiophene analogs mitigates the acrylamide induced oxidative stress in the zebrafish larvae by stabilizing the glutathione redox cycle. Life Sci 2022; 298:120507. [PMID: 35358593 DOI: 10.1016/j.lfs.2022.120507] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 03/18/2022] [Accepted: 03/24/2022] [Indexed: 01/08/2023]
Abstract
AIMS This study aims to elucidate a systematic free-radical quenching ability of synthesized benzo[b]thiophene derivatives using in vitro assays and acrylamide induced oxidatively stressed model in zebrafish larvae. MATERIALS AND METHODS Antioxidant activity of the compounds was evaluated using in vitro methods. The toxicity of the compounds was evaluated in Madin-Darby Canine Kidney (MDCK) cell line and zebrafish embryos. Oxidative stress was generated by acrylamide (1 mM) in zebrafish larvae and treated with compounds to evaluate the in vivo antioxidant ability. Specific fluorescence dyes were used to detect ROS generation, lipid peroxidation, and cell death followed by gene expression using RT PCR. Density functional theory (DFT) and in silico pharmacokinetics were also studied. KEY FINDINGS Compound BP and EP have a greater in vitro free radical scavenging ability. The maximum tolerated concentration (MTC) of the compounds in zebrafish larvae is 80 μM. The antioxidant system in zebrafish larvae was dysregulated due to acrylamide exposure and improvement was found while treating acrylamide exposed larvae with compounds 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP). Compound BP and EP enhanced the SOD and CAT activity, reduced the ROS and lipid peroxidation level, thus decreasing cell death in zebrafish larvae. Compound BP and EP also improved the glutathione redox cycle by stabilizing glutathione-related gene expressions. SIGNIFICANCE Hydroxyl-containing compounds BP and EP are promising lead molecules for pathological conditions related to oxidative stress, which showed an attenuated effect on acrylamide-induced oxidative stress in zebrafish larvae by enhancing the glutathione redox cycle and enzymatic antioxidants.
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Affiliation(s)
- B Haridevamuthu
- Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India
| | - Tamilvelan Manjunathan
- Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India
| | - Ajay Guru
- Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India
| | - Rajendran Saravana Kumar
- Chemistry Division, School of Advanced Sciences, VIT University, Chennai Campus, Chennai 600 127, Tamil Nadu, India
| | - Rajakrishnan Rajagopal
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Palaniselvam Kuppusamy
- Department of Animal Biotechnology, Jeonbuk National University, Jeonju 54896, South Korea
| | - Annie Juliet
- Institute for Cellular and Molecular Biology, The University of Texas at Austin, 1 University Station A4800, Austin, TX 78712, USA
| | - Pushparathinam Gopinath
- Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
| | - Jesu Arockiaraj
- Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
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13
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Yazdandoust S, Parizadeh SMR, Ghayour-Mobarhan M, Yaghmaei P, Sahebkar AH. High-density lipoprotein lipid peroxidation as a diagnostics biomarker in coronary artery disease. Biofactors 2022; 48:634-642. [PMID: 35080064 DOI: 10.1002/biof.1819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/02/2021] [Indexed: 11/12/2022]
Abstract
This study aimed at evaluating the serum High-density lipoprotein lipid peroxidation (HDLox) levels and their association with coronary artery disease (CAD). This case-control study comprised 572 patients with stable CAD and 281 healthy subjects with no history of cardiovascular disease (control group). Based on the results of coronary angiography, the patient group was divided into two groups: CAD- and CAD+. HDLox was measured using a fluorimetric method. The ability of HDLox and serum high-density lipoprotein cholesterol (HDL-C) to detect CAD and coronary artery stenosis ≥50% was also compared using the receiver operating characteristic (ROC) curve analysis. The CAD patients showed significantly higher serum HDLox levels, compared to the control group [1.15 (1.01-1.31) vs. 0.85 (0.62-1.06), no units, p < 0.001]. Moreover, serum HDLox levels were significantly lower in CAD- patients, compared to the CAD+ patients [1.05 (0.92-1.22) vs. 1.24 (1.12-1.35), no units, p < 0.001]. According to the results of univariate and multivariate logistic regression, the HDLox showed association with the presence of CAD (odds ratio [OR]: 1.754; 95% confidence interval [CI]: 1.564-1.968; p < 0.001) and coronary artery stenosis ≥50% (OR: 1.729; 95% CI: 1.534-1.949; p < 0.001). The results obtained from the area under the ROC curve revealed that the HDLox could better detect the risk of CAD and coronary artery stenosis ≥50% compared to serum HDL-C level. The oxidation of HDL leads to a reduction in its antioxidant function and it has a crucial role in the development of atherosclerosis. HDLox is suggested as a diagnostics biomarker for CAD.
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Affiliation(s)
- Shima Yazdandoust
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Majid Ghayour-Mobarhan
- Iranian UNESCO center of excellence for human nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parichehreh Yaghmaei
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Amir Hossein Sahebkar
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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14
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Mohan Manu T, Anand T, Sharath Babu GR, Patil MM, Khanum F. Bacopa monniera extract mitigates isoproterenol-induced cardiac stress via Nrf2/Keap1/NQO1 mediated pathway. Arch Physiol Biochem 2022; 128:341-351. [PMID: 31755309 DOI: 10.1080/13813455.2019.1683583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The present study was aimed to investigate the effect of standardised hydroalcoholic extract of Bacopa monniera (BME) against isoproterenol (ISO) induced cardiac stress. Isoproterenol (85 mg/kg body weight) was administered intraperitoneally to induce cardiac stress in rats. Bacopa monniera extract (BME75 and 150 mg/kg) was orally administered for 21 days followed by ISO on 22nd and 23rd experimental days. ISO caused significant cardiac damage, which was concomitant with increased apoptosis and attenuated expressions of Nrf2, HO-1, and regulating apoptotic protein expressions of Bax, Bcl2 and NOS2. Treatment with BME in rats significantly improved cardiac dysfunction by maintaining cardiac rhythm, myocardial integrity. Decreased oxidative stress by restored expressions of Nrf2, NQO1 and HO-1 followed by elevating antioxidant enzymes and total glutathione levels. Our present results suggest that the BME treatment strengthening the endogenous defence system through Nrf2 modulation and played a key role against cardiac oxidative stress induced by ISO in rats.
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Affiliation(s)
- T Mohan Manu
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, India
| | - T Anand
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, India
| | - G R Sharath Babu
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, India
| | - Mahantesh M Patil
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, India
| | - Farhath Khanum
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, India
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15
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Role of puerarin in pathological cardiac remodeling: A review. Pharmacol Res 2022; 178:106152. [DOI: 10.1016/j.phrs.2022.106152] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/28/2022] [Accepted: 03/01/2022] [Indexed: 12/22/2022]
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16
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Strath LJ, Sorge RE. Racial Differences in Pain, Nutrition, and Oxidative Stress. Pain Ther 2022; 11:37-56. [PMID: 35106711 PMCID: PMC8861224 DOI: 10.1007/s40122-022-00359-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/21/2022] [Indexed: 12/12/2022] Open
Abstract
Investigating the disproportionate rates of chronic pain and their related comorbidities between Black and non-Hispanic White (White) individuals is a growing area of interest, both in the healthcare community and in general society. Researchers have identified racial differences in chronic pain prevalence and severity, but still very little is known about the mechanisms underlying them. Current explanations for these differences have primarily focused on socioeconomic status and unequal healthcare between races as causal factors. Whereas these factors are informative, a racial gap still exists between Black and White individuals when these factors are controlled for. One potential cause of this racial gap in chronic pain is the differences in nutrition and dietary intake between groups. Certain foods play a key role in the inflammatory and oxidative stress pathways in the human body and could potentially influence the severity of the pain experience. Here, we review the previous literature on the surrounding topics and propose a potential mechanism to explain racial differences in the chronic pain population, based on established racial differences in diet and oxidative stress.
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Affiliation(s)
- Larissa J Strath
- Department of Psychology, The University of Alabama at Birmingham, 1300 University Blvd, Birmingham, AL, 35294, USA
| | - Robert E Sorge
- Department of Psychology, The University of Alabama at Birmingham, 1300 University Blvd, Birmingham, AL, 35294, USA.
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17
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The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27010273. [PMID: 35011505 PMCID: PMC8747024 DOI: 10.3390/molecules27010273] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 12/21/2021] [Accepted: 12/22/2021] [Indexed: 12/20/2022]
Abstract
Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use.
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18
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Lee WJ, Lee SH. Protocatechuic acid protects hepatocytes against hydrogen peroxide-induced oxidative stress. Curr Res Food Sci 2022; 5:222-227. [PMID: 35106486 PMCID: PMC8789513 DOI: 10.1016/j.crfs.2022.01.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/07/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress is a main cause of tissue damage and highly associated with incidence of human chronic diseases. Among the major target organs attacked by reactive oxygen species (ROS) is the liver. Protocatechuic acid (PCA) is a phenolic compound found in green tea, acai oil and some mushroom species that possesses strong antioxidative and anti-inflammatory activity and may have benefits as a natural phytochemical for prevention of human diseases. However, the protective effect of PCA on hydrogen peroxide (H2O2)-induced oxidative stress specifically in the liver has not yet been investigated. The current study aims to observe if PCA possesses protective activity against H2O2-induced oxidative stress in HepG2 human liver cancer cells. Relative to untreated control cells, treatment of HepG2 cells with PCA reduced H2O2-induced cell death and mitigated H2O2-induced production of ROS; furthermore, it mitigated the H2O2-induced increase of caspase-3/7 enzyme activity, expression of cleaved poly(ADP-ribose) polymerase (PARP), expression of endoplasmic reticulum (ER) stress genes including activating transcription factor 4 (ATF4), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). These findings indicate that PCA effectively protects hepatic cells from H2O2-induced oxidative stress and cell death.
Protocatechuic acid restored hydrogen peroxide-induced suppression of cell viability. Protocatechuic acid mitigated hydrogen peroxide-induced generation of reactive oxygen species. Protocatechuic acid mitigated hydrogen peroxide-induced apoptosis and endoplasmic reticulum stress.
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19
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Bohling R, Grafals M, Moreau K, You Z, Tommerdahl KL, Bjornstad P, Stenson EK, Andrews E, Ramirez-Renteria L, Kendrick J. A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients. Kidney Int Rep 2021; 6:2323-2330. [PMID: 34514193 PMCID: PMC8419116 DOI: 10.1016/j.ekir.2021.06.006] [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: 01/28/2021] [Revised: 05/18/2021] [Accepted: 06/07/2021] [Indexed: 12/31/2022] Open
Abstract
Introduction Metabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs. Methods We performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo. Results Twenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI -0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate. Conclusions Sodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial.
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Affiliation(s)
- Rachel Bohling
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Monica Grafals
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kerrie Moreau
- Division of Geriatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Eastern Colorado VA Geriatric Research, Education and Clinical Center, Aurora, Colorado, USA
| | - Zhiying You
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kalie L Tommerdahl
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Petter Bjornstad
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Erin K Stenson
- Department of Pediatrics, Section of Critical Care Medicine, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Emily Andrews
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Lorena Ramirez-Renteria
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jessica Kendrick
- Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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20
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Mouchel Dit Leguerrier D, Barré R, Ruet Q, Imbert D, Philouze C, Fries PH, Martel-Frachet V, Molloy JK, Thomas F. Lanthanide complexes of DOTA-nitroxide conjugates for redox imaging: spectroelectrochemistry, CEST, relaxivity, and cytotoxicity. Dalton Trans 2021; 50:10826-10837. [PMID: 34291274 DOI: 10.1039/d1dt01628h] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The lanthanide(iii) complexes (Gd, Eu, Dy, and Yb) of DOTA tris(amide) and bis(amide) derivatives (L1 and L2) featuring one redox active TEMPO arm were prepared. Ligand L2 harbours an alkyne fragment for further functionalization. The X-ray crystal structure of ligand L2 in complexation with Na+ was solved. The complexes showed in their CV one oxidation wave (0.26-0. 34 V vs. Fc+/Fc) due to an oxoammonium/nitroxide redox couple and a broad reduction corresponding to the nitroxide/hydroxylamine system. The Eu complexes demonstrated the presence of one water molecule in their coordination sphere. The nitroxide complexes were characterized by EPR spectroscopy, showing the typical 3-line pattern in the high temperature regime, which is quenched upon the addition of ascorbate (reduction into hydroxylamine). In their nitroxide form, the complexes show essentially no CEST peak. Conversely, the reduced complexes demonstrate a 12% CEST peak at 51 ppm, corresponding to the metal bound water molecule. Fast exchange precluded the CEST activity for the amide protons. All the complexes proved to be essentially non-toxic for M21 cells at concentrations up to 50 μM.
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Affiliation(s)
| | - R Barré
- Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France.
| | - Q Ruet
- Institute for Advanced Biosciences, INSERM U1209, UMR CNRS 5309, Grenoble Alpes University, 38700 La Tronche, France
| | - D Imbert
- Univ. Grenoble Alpes, CEA, CNRS, IRIG-LCBM, 38000 Grenoble, France
| | - C Philouze
- Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France.
| | - P H Fries
- Univ. Grenoble Alpes, CEA, CNRS, IRIG-LCBM, 38000 Grenoble, France
| | - V Martel-Frachet
- Institute for Advanced Biosciences, INSERM U1209, UMR CNRS 5309, Grenoble Alpes University, 38700 La Tronche, France and EPHE, PSL Research University, 75014 Paris, France
| | - J K Molloy
- Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France.
| | - F Thomas
- Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France.
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21
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Oxygen‐derived free radicals: Production, biological importance, bioimaging, and analytical detection with responsive luminescent nanoprobes. VIEW 2021. [DOI: 10.1002/viw.20200139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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22
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Zhang H, Zhang RH, Liao XM, Yang D, Wang YC, Zhao YL, Xu GB, Liu CH, Li YJ, Liao SG, Zhou M. Discovery of β-Carboline Derivatives as a Highly Potent Cardioprotectant against Myocardial Ischemia-Reperfusion Injury. J Med Chem 2021; 64:9166-9181. [PMID: 34132541 DOI: 10.1021/acs.jmedchem.1c00384] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Timely myocardial reperfusion salvages ischemic myocardium from infarction, whereas reperfusion itself induces cardiomyocyte death, which is called myocardial ischemia/reperfusion (MI/R) injury. Herein, β-carboline derivative 17c was designed and synthesized with obvious myocardial protective activity for the first time. Pretreatment of 17c effectively protected the cardiomyocyte H9c2 cells from H2O2-induced lactate dehydrogenase leakage and restored the endogenous antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Besides, 17c effectively protected the mitochondria through decreasing the reactive oxygen species overproduction and enhancing the mitochondrial membrane potential. As a result, 17c significantly reduced the necrosis of cardiomyocytes in H2O2-induced oxidative stress, which was more potent than polydatin. In MI/R injury rats, 17c pretreatment obviously increased the levels of SOD and GSH-Px and inhibited the apoptosis of cardiomyocytes. Through this way, the size of myocardial infarction was significantly reduced after MI/R injury in vivo, better than that of polydatin, suggesting that 17c is a promising cardioprotectant for the prevention of MI/R injury.
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Affiliation(s)
- Hong Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, P. R. China.,School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Rong-Hong Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, P. R. China.,Center for Tissue Engineering and Stem Cell Research, Key Laboratory of Regenerative Medicine of Guizhou Province, Guizhou Medical University, Guiyang 550004, P. R. China
| | - Xiang-Ming Liao
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Dan Yang
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Yu-Chan Wang
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Yong-Long Zhao
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Guo-Bo Xu
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Chun-Hua Liu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, P. R. China.,School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Yong-Jun Li
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, P. R. China.,School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Shang-Gao Liao
- School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
| | - Meng Zhou
- State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, P. R. China.,School of Pharmacy, Guizhou Medical University, Guian New District, , Guizhou 550025, P. R. China
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23
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Ali MY, Zaib S, Jannat S, Khan I. Inhibition of Angiotensin-I Converting Enzyme by Ginsenosides: Structure-Activity Relationships and Inhibitory Mechanism. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:6073-6086. [PMID: 34014666 DOI: 10.1021/acs.jafc.1c01231] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Ginseng (Panax ginseng C. A. Meyer) extract has been reported to inhibit the angiotensin converting enzyme (ACE); however, the possible inhibitory action of most of its constituents (ginsenosides) against ACE remains unknown. Thus, in this study, we investigated ginsenoside derivatives' inhibitory effect on ACE. We assessed the activities of 22 ginsenosides, most of which inhibited ACE significantly. Notably, protopanaxatriol, protopanaxadiol, and ginsenoside Rh2 exhibited the most potent ACE inhibitory potential, with IC50 values of 1.57, 2.22, and 5.60 μM, respectively. Further, a kinetic study revealed different modes of inhibition against ACE. Molecular docking studies have confirmed that ginsenosides inhibit ACE via many hydrogen bonds and hydrophobic interactions with catalytic residues and zinc ion of C- and N-domain ACE that block the catalytic activity of ACE. In addition, we found that the active ginsenosides stimulated glucose uptake in insulin-resistant C2C12 skeletal muscle cells in a dose-dependent manner. Moreover, the most active ginsenosides' reactive oxygen species (ROS) and peroxynitrite (ONOO-) scavenging properties were evaluated, in which IC50 values ranged from 1.44-43.83 to 2.36-39.56 μM in ONOO- and ROS, respectively. The results derived from these computational and in vitro experiments provide additional scientific support for the anecdotal use of ginseng in traditional medicine to treat cardiovascular diseases such as hypertension.
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Affiliation(s)
- Md Yousof Ali
- Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Sumera Zaib
- Department of Biochemistry, Faculty of Life Sciences, University of Central Punjab, Lahore 54590, Pakistan
| | - Susoma Jannat
- Department of Biochemistry and Molecular Biology, University of Calgary, T2N 1N4 Alberta, Canada
| | - Imtiaz Khan
- Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
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24
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Vardakas P, Skaperda Z, Tekos F, Trompeta AF, Tsatsakis A, Charitidis CA, Kouretas D. An integrated approach for assessing the in vitro and in vivo redox-related effects of nanomaterials. ENVIRONMENTAL RESEARCH 2021; 197:111083. [PMID: 33775680 DOI: 10.1016/j.envres.2021.111083] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/22/2021] [Accepted: 03/22/2021] [Indexed: 06/12/2023]
Abstract
Over the last few decades, nanotechnology has risen to the forefront of both the research and industrial interest, resulting in the manufacture and utilization of various nanomaterials, as well as in their integration into a wide range of fields. However, the consequent elevated exposure to such materials raises serious concerns regarding their effects on human health and safety. Existing scientific data indicate that the induction of oxidative stress, through the excessive generation of Reactive Oxygen Species (ROS), might be the principal mechanism of exerting their toxicity. Meanwhile, a number of nanomaterials exhibit antioxidant properties, either intrinsic or resulting from their functionalization with conventional antioxidants. Considering that their redox properties are implicated in the manifestation of their biological effects, we propose an integrated approach for the assessment of the redox-related activities of nanomaterials at three biological levels (in vitro-cell free systems, cell cultures, in vivo). Towards this direction, a battery of translational biomarkers is recommended, and a series of reliable protocols are presented in detail. The aim of the present approach is to acquire a better understanding with respect to the biological actions of nanomaterials in the interrelated fields of Redox Biology and Toxicology.
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Affiliation(s)
- Periklis Vardakas
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500, Larissa, Greece
| | - Zoi Skaperda
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500, Larissa, Greece
| | - Fotios Tekos
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500, Larissa, Greece
| | - Aikaterini-Flora Trompeta
- Research Lab of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechniou St. Zografos, 157 80, Athens, Greece
| | - Aristidis Tsatsakis
- Laboratory of Toxicology Science and Research, Medical School, University of Crete, 71003, Heraklion, Crete, Greece
| | - Constantinos A Charitidis
- Research Lab of Advanced, Composite, Nano-Materials and Nanotechnology, School of Chemical Engineering, National Technical University of Athens, 9 Heroon Polytechniou St. Zografos, 157 80, Athens, Greece
| | - Demetrios Kouretas
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500, Larissa, Greece.
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Effect of Reactive Oxygen Species on the Endoplasmic Reticulum and Mitochondria during Intracellular Pathogen Infection of Mammalian Cells. Antioxidants (Basel) 2021; 10:antiox10060872. [PMID: 34071633 PMCID: PMC8229183 DOI: 10.3390/antiox10060872] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/24/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
Oxidative stress, particularly reactive oxygen species (ROS), are important for innate immunity against pathogens. ROS directly attack pathogens, regulate and amplify immune signals, induce autophagy and activate inflammation. In addition, production of ROS by pathogens affects the endoplasmic reticulum (ER) and mitochondria, leading to cell death. However, it is unclear how ROS regulate host defense mechanisms. This review outlines the role of ROS during intracellular pathogen infection, mechanisms of ROS production and regulation of host defense mechanisms by ROS. Finally, the interaction between microbial pathogen-induced ROS and the ER and mitochondria is described.
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Hong MY, Kern M, Nakamichi-Lee M, Abbaspour N, Ahouraei Far A, Hooshmand S. Dried Plum Consumption Improves Total Cholesterol and Antioxidant Capacity and Reduces Inflammation in Healthy Postmenopausal Women. J Med Food 2021; 24:1161-1168. [PMID: 33978491 DOI: 10.1089/jmf.2020.0142] [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] [Indexed: 12/24/2022] Open
Abstract
Dried plums contain bioactive components that have demonstrated antioxidant and anti-inflammatory effects. The objective of this study was to determine if dried plum consumption reduces the risk factors for cardiovascular disease (CVD) in postmenopausal women, specifically examining lipid profiles, oxidative stress, antioxidant capacity, and inflammation in a dose-dependent manner. We conducted a 6-month, parallel-design controlled clinical trial, where 48 postmenopausal women were randomly assigned to consume 0, 50, or 100 g of dried plum each day. After 6 months of intervention, total cholesterol (TC) in the 100 g/day treatment group (P = .002) and high-density lipoprotein cholesterol in the 50 g/day treatment group (P = .005) improved significantly compared to baseline. Inflammatory biomarkers interleukin-6 (P = .044) and tumor necrosis factor-α (P = .040) were significantly lower after 6 months within the 50 g/day dried plum group compared to baseline. Moreover, total antioxidant capacity increased significantly within the 50 g/day group (P = .046), and superoxide dismutase activity increased significantly within both 50 and 100 g/day groups (P = .044 and P = .027, respectively) after 6 months compared to baseline. In addition, plasma activities of alanine transaminase (P = .046), lactate dehydrogenase (P = .039), and creatine kinase (P = .030) were significantly lower after 6 months in the 50 g/day dried plum group. These findings suggest that daily consumption of 50-100 g dried plum improves CVD risk factors in postmenopausal women as exhibited by lower TC, oxidative stress, and inflammatory markers with no clear dose dependence.
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Affiliation(s)
- Mee Young Hong
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Mark Kern
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Michelle Nakamichi-Lee
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Nazanin Abbaspour
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Arshya Ahouraei Far
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Shirin Hooshmand
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
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27
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Wirth A, Wolf B, Huang CK, Glage S, Hofer SJ, Bankstahl M, Bär C, Thum T, Kahl KG, Sigrist SJ, Madeo F, Bankstahl JP, Ponimaskin E. Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length. GeroScience 2021; 43:673-690. [PMID: 33517527 PMCID: PMC8110654 DOI: 10.1007/s11357-020-00310-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 12/02/2020] [Indexed: 12/17/2022] Open
Abstract
Ageing provokes a plethora of molecular, cellular and physiological deteriorations, including heart failure, neurodegeneration, metabolic maladaptation, telomere attrition and hair loss. Interestingly, on the molecular level, the capacity to induce autophagy, a cellular recycling and cleaning process, declines with age across a large spectrum of model organisms and is thought to be responsible for a subset of age-induced changes. Here, we show that a 6-month administration of the natural autophagy inducer spermidine in the drinking water to aged mice is sufficient to significantly attenuate distinct age-associated phenotypes. These include modulation of brain glucose metabolism, suppression of distinct cardiac inflammation parameters, decreased number of pathological sights in kidney and liver and decrease of age-induced hair loss. Interestingly, spermidine-mediated age protection was associated with decreased telomere attrition, arguing in favour of a novel cellular mechanism behind the anti-ageing effects of spermidine administration.
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Affiliation(s)
- Alexander Wirth
- Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Bettina Wolf
- Preclinical Molecular Imaging, Department of Nuclear Medicine, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Cheng-Kai Huang
- Institute of Molecular and Translational Therapeutic Strategies, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Silke Glage
- Institute for Laboratory Animal Science, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Sebastian J Hofer
- Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Humboldtstraße 50/EG, 8010, Graz, Austria
| | - Marion Bankstahl
- Institute for Laboratory Animal Science, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Christian Bär
- Institute of Molecular and Translational Therapeutic Strategies, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
- REBIRTH Center for Translational Regenerative Medicine, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
- REBIRTH Center for Translational Regenerative Medicine, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
- Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Straße 1, 30625, Hannover, Germany
| | - Kai G Kahl
- Dept. of Psychiatry; Social Psychiatry and Psychotherapy, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Stephan J Sigrist
- Freie University Berlin, Institute of Biology, Takusstraße 6, 14195, Berlin, Germany
| | - Frank Madeo
- Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Humboldtstraße 50/EG, 8010, Graz, Austria
| | - Jens P Bankstahl
- Preclinical Molecular Imaging, Department of Nuclear Medicine, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
| | - Evgeni Ponimaskin
- Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
- Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, Gagarin ave. 23, Nizhny Novgorod, Russian Federation, 603950.
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Mohs A, Otto T, Schneider KM, Peltzer M, Boekschoten M, Holland CH, Hudert CA, Kalveram L, Wiegand S, Saez-Rodriguez J, Longerich T, Hengstler JG, Trautwein C. Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis. J Hepatol 2021; 74:638-648. [PMID: 33342543 DOI: 10.1016/j.jhep.2020.09.037] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 09/25/2020] [Accepted: 09/29/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS In chronic liver diseases, inflammation induces oxidative stress and thus may contribute to the progression of liver injury, fibrosis, and carcinogenesis. The KEAP1/NRF2 axis is a major regulator of cellular redox balance. In the present study, we investigated whether the KEAP1/NRF2 system is involved in liver disease progression in humans and mice. METHODS The clinical relevance of oxidative stress was investigated by liver RNA sequencing in a well-characterized cohort of patients with non-alcoholic fatty liver disease (n = 63) and correlated with histological and clinical parameters. For functional analysis, hepatocyte-specific Nemo knockout (NEMOΔhepa) mice were crossed with hepatocyte-specific Keap1 knockout (KEAP1Δhepa) mice. RESULTS Immunohistochemical analysis of human liver sections showed increased oxidative stress and high NRF2 expression in patients with chronic liver disease. RNA sequencing of liver samples in a human pediatric NAFLD cohort revealed a significant increase of NRF2 activation correlating with the grade of inflammation, but not with the grade of steatosis, which could be confirmed in a second adult NASH cohort. In mice, microarray analysis revealed that Keap1 deletion induces NRF2 target genes involved in glutathione metabolism and xenobiotic stress (e.g., Nqo1). Furthermore, deficiency of one of the most important antioxidants, glutathione (GSH), in NEMOΔhepa livers was rescued after deleting Keap1. As a consequence, NEMOΔhepa/KEAP1Δhepa livers showed reduced apoptosis compared to NEMOΔhepa livers as well as a dramatic downregulation of genes involved in cell cycle regulation and DNA replication. Consequently, NEMOΔhepa/KEAP1Δhepa compared to NEMOΔhepa livers displayed decreased fibrogenesis, lower tumor incidence, reduced tumor number, and decreased tumor size. CONCLUSIONS NRF2 activation in patients with non-alcoholic steatohepatitis correlates with the grade of inflammation, but not steatosis. Functional analysis in mice demonstrated that NRF2 activation in chronic liver disease is protective by ameliorating fibrogenesis, initiation and progression of hepatocellular carcinogenesis. LAY SUMMARY The KEAP1 (Kelch-like ECH-associated protein-1)/NRF2 (erythroid 2-related factor 2) axis has a major role in regulating cellular redox balance. Herein, we show that NRF2 activity correlates with the grade of inflammation in patients with non-alcoholic steatohepatitis. Functional studies in mice actually show that NRF2 activation, resulting from KEAP1 deletion, protects against fibrosis and cancer.
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Affiliation(s)
- Antje Mohs
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tobias Otto
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Kai Markus Schneider
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Mona Peltzer
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Mark Boekschoten
- Department of Agrotechnology and Food Sciences, University Wageningen, Wageningen, the Netherlands
| | - Christian H Holland
- Faculty of Medicine, Institute of Computational Biomedicine, Heidelberg University, Bioquant, Heidelberg, Germany; Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Aachen, Germany; Systems Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany
| | - Christian A Hudert
- Department of Pediatric Gastroenterology, Charité - Universitätsmedizin Berlin, Germany
| | - Laura Kalveram
- Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Susanna Wiegand
- Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Julio Saez-Rodriguez
- Faculty of Medicine, Institute of Computational Biomedicine, Heidelberg University, Bioquant, Heidelberg, Germany; Faculty of Medicine, Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Aachen, Germany
| | - Thomas Longerich
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Jan G Hengstler
- Systems Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany
| | - Christian Trautwein
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
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29
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Silva C, Pinto M, Fernandes C, Benfeito S, Borges F. Antioxidant Therapy and Neurodegenerative Disorders: Lessons From Clinical Trials. SYSTEMS MEDICINE 2021. [DOI: 10.1016/b978-0-12-801238-3.11611-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Kim JW, Jo EH, Moon JE, Cha H, Chang MH, Cho HT, Lee MK, Jung WS, Lee JH, Heo W, Kim YJ. In Vitro and In Vivo Inhibitory Effect of Citrus Junos Tanaka Peel Extract against Oxidative Stress-Induced Apoptotic Death of Lung Cells. Antioxidants (Basel) 2020; 9:E1231. [PMID: 33291640 PMCID: PMC7761914 DOI: 10.3390/antiox9121231] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 12/27/2022] Open
Abstract
Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H2O2. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.
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Affiliation(s)
- Jin Woo Kim
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Eun Hee Jo
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Ji Eun Moon
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Hanvit Cha
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Moon Han Chang
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Hyung Taek Cho
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Min Kook Lee
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
| | - Wan Sik Jung
- Immunotech, Inc., Cheonan-si, Chungnam 31094, Korea;
| | - Jin Hyup Lee
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
- Institutes of Natural Sciences, Korea University, Sejong 8244, Korea
| | - Wan Heo
- Institutes of Natural Sciences, Korea University, Sejong 8244, Korea
| | - Young Jun Kim
- Department of Food and Biotechnology, Korea University, Sejong 8244, Korea; (J.W.K.); (E.H.J.); (J.E.M.); (H.C.); (M.H.C.); (H.T.C.); (M.K.L.)
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31
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Zhang J, Sun P, Zhou C, Zhang X, Ma F, Xu Y, Hamblin MH, Yin K. Regulatory microRNAs and vascular cognitive impairment and dementia. CNS Neurosci Ther 2020; 26:1207-1218. [PMID: 33459504 PMCID: PMC7702235 DOI: 10.1111/cns.13472] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/11/2022] Open
Abstract
Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post-transcriptional level. As small endogenous non-coding RNAs, microRNAs (miRs) can regulate target gene expression through post-transcriptional gene silencing. miRs have been reported to play an important role in the pathology of VCID and have recently been suggested as potential novel pharmacological targets for the development of new diagnosis and treatment strategies in VCID. In this review, we summarize the current understanding of VCID, the possible role of miRs in the regulation of VCID and attempt to envision future therapeutic strategies. Since manipulation of miR levels by either pharmacological or genetic approaches has shown therapeutic effects in experimental VCID models, we also emphasize the potential therapeutic value of miRs in clinical settings.
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Affiliation(s)
- Jing Zhang
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Ping Sun
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Chao Zhou
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Xuejing Zhang
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Feifei Ma
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Yang Xu
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
| | - Milton H. Hamblin
- Department of PharmacologyTulane University School of MedicineNew OrleansLAUSA
| | - Ke‐Jie Yin
- Department of NeurologyPittsburgh Institute of Brain Disorders & RecoveryUniversity of Pittsburgh School of MedicinePittsburghPAUSA
- Geriatric ResearchEducation and Clinical CenterVeterans Affairs Pittsburgh Healthcare SystemPittsburghPAUSA
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Burns M, Rizvi SHM, Tsukahara Y, Pimentel DR, Luptak I, Hamburg NM, Matsui R, Bachschmid MM. Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases. Int J Mol Sci 2020; 21:E6803. [PMID: 32948023 PMCID: PMC7555996 DOI: 10.3390/ijms21186803] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/09/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular diseases are the leading cause of death worldwide, and as rates continue to increase, discovering mechanisms and therapeutic targets become increasingly important. An underlying cause of most cardiovascular diseases is believed to be excess reactive oxygen or nitrogen species. Glutathione, the most abundant cellular antioxidant, plays an important role in the body's reaction to oxidative stress by forming reversible disulfide bridges with a variety of proteins, termed glutathionylation (GSylation). GSylation can alter the activity, function, and structure of proteins, making it a major regulator of cellular processes. Glutathione-protein mixed disulfide bonds are regulated by glutaredoxins (Glrxs), thioltransferase members of the thioredoxin family. Glrxs reduce GSylated proteins and make them available for another redox signaling cycle. Glrxs and GSylation play an important role in cardiovascular diseases, such as myocardial ischemia and reperfusion, cardiac hypertrophy, peripheral arterial disease, and atherosclerosis. This review primarily concerns the role of GSylation and Glrxs, particularly glutaredoxin-1 (Glrx), in cardiovascular diseases and the potential of Glrx as therapeutic agents.
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Affiliation(s)
- Mannix Burns
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
| | - Syed Husain Mustafa Rizvi
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
- Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (D.R.P.); (I.L.)
| | - Yuko Tsukahara
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
| | - David R. Pimentel
- Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (D.R.P.); (I.L.)
| | - Ivan Luptak
- Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (D.R.P.); (I.L.)
| | - Naomi M. Hamburg
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
- Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (D.R.P.); (I.L.)
| | - Reiko Matsui
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
| | - Markus M. Bachschmid
- Vascular Biology Section, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St., Boston, MA 02118, USA; (M.B.); (S.H.M.R.); (Y.T.); (N.M.H.); (M.M.B.)
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Qi Z, Zhang Y, Chen ZF, Yang C, Song Y, Liao X, Li W, Tsang SY, Liu G, Cai Z. Chemical identity and cardiovascular toxicity of hydrophobic organic components in PM 2.5. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 201:110827. [PMID: 32535366 DOI: 10.1016/j.ecoenv.2020.110827] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/25/2020] [Accepted: 05/27/2020] [Indexed: 06/11/2023]
Abstract
Numerous experimental and epidemiological studies have demonstrated that exposure to PM2.5 may result in pathogenesis of several major cardiovascular diseases (CVDs), which can be attributed to the combined adverse effects induced by the complicated components of PM2.5. Organic materials, which are major components of PM2.5, contain thousands of chemicals, and most of them are environmental hazards. However, the contamination profile and contribution to overall toxicity of PM2.5-bound organic components (OCs) have not been thoroughly evaluated yet. Herein, we aim to provide an overview of the literature on PM2.5-bound hydrophobic OCs, with an emphasis on the chemical identity and reported impairments on the cardiovascular system, including the potential exposure routes and mechanisms. We first provide an update on the worldwide mass concentration and composition data of PM2.5, and then, review the contamination profile of PM2.5-bound hydrophobic OCs, including constitution, concentration, distribution, formation, source, and identification. In particular, the link between exposure to PM2.5-bound hydrophobic OCs and CVDs and its possible underlying mechanisms are discussed to evaluate the possible risks of PM2.5-bound hydrophobic OCs on the cardiovascular system and to provide suggestions for future studies.
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Affiliation(s)
- Zenghua Qi
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Yanhao Zhang
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
| | - Zhi-Feng Chen
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Chun Yang
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Yuanyuan Song
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
| | - Xiaoliang Liao
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Weiquan Li
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Suk Ying Tsang
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Guoguang Liu
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
| | - Zongwei Cai
- Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
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Ghafouri-Fard S, Shoorei H, Taheri M. Non-coding RNAs are involved in the response to oxidative stress. Biomed Pharmacother 2020; 127:110228. [DOI: 10.1016/j.biopha.2020.110228] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 04/20/2020] [Accepted: 05/03/2020] [Indexed: 01/17/2023] Open
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Piotrowicz IBB, Garcés-Rimón M, Moreno-Fernández S, Aleixandre A, Salas-Mellado M, Miguel-Castro M. Antioxidant, Angiotensin-Converting Enzyme Inhibitory Properties and Blood-Pressure-Lowering Effect of Rice Bran Protein Hydrolysates. Foods 2020; 9:E812. [PMID: 32575679 PMCID: PMC7353587 DOI: 10.3390/foods9060812] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 11/16/2022] Open
Abstract
This research aimed to investigate the biological properties of different hydrolysates derived from industrial and laboratory defatted rice bran proteins. Industrial and laboratory defatted rice bran protein concentrates were hydrolyzed with alcalase or flavorzyme. The degree of hydrolysis (DH), oxygen radical absorbance capacity (ORAC), reducing power, total phenolic compounds (TPC), and angiotensin-converting enzyme (ACE) inhibitory activity, were determined in the hydrolysates and the molecular fractions lower than 3 kDa. Systolic blood pressure (SBP) was measured using the tail-cuff method before and after oral administration of 80 mg/kg of different rice bran protein hydrolysate (RBPH) fractions lower than 3 kDa in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The highest values of in vitro antioxidant activity and TPC were observed in RBPH with alcalase defatted by industry (RBPH2A), and, in all cases, these bioactivities were higher in the molecular fractions lower than 3 kDa. Once again, fractions lower than 3 kDa obtained with alcalase showed a potent ACE inhibitory activity (RBPH1A<3 and RBPH2A<3). The administration of RBPH1A<3 caused a significant decrease in the SBP in SHR, where the maximum decrease was reached at 8 h after administration. SBP in WKY rats was not modified after the administration of RBPH1A<3. These results suggest that the rice bran protein hydrolysates obtained from industry after treatment with alcalase could be an interesting source of bioactive peptides, with potential action on hypertension and other related pathologies.
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Affiliation(s)
- Inajara Beatriz Brose Piotrowicz
- Laboratório de Tecnologia de Alimentos, Escola de Química e Alimentos, Universidade Federal do Rio Grande, Rio Grande 96.203-900, Brasil; (I.B.B.P.); (M.S.-M.)
- Departamento de Bioactividad y Análisis de Alimentos, Instituto de Investigación en Ciencia de Alimentación (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.G.-R.); (S.M.-F.)
| | - Marta Garcés-Rimón
- Departamento de Bioactividad y Análisis de Alimentos, Instituto de Investigación en Ciencia de Alimentación (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.G.-R.); (S.M.-F.)
- Grupo de Investigación en Biotecnología Alimentaria, Universidad Francisco de Vitoria, 28223 Madrid, Spain
| | - Silvia Moreno-Fernández
- Departamento de Bioactividad y Análisis de Alimentos, Instituto de Investigación en Ciencia de Alimentación (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.G.-R.); (S.M.-F.)
| | - Amaya Aleixandre
- Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Myriam Salas-Mellado
- Laboratório de Tecnologia de Alimentos, Escola de Química e Alimentos, Universidade Federal do Rio Grande, Rio Grande 96.203-900, Brasil; (I.B.B.P.); (M.S.-M.)
| | - Marta Miguel-Castro
- Departamento de Bioactividad y Análisis de Alimentos, Instituto de Investigación en Ciencia de Alimentación (CIAL, CSIC-UAM), 28049 Madrid, Spain; (M.G.-R.); (S.M.-F.)
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Saheera S, Krishnamurthy P. Cardiovascular Changes Associated with Hypertensive Heart Disease and Aging. Cell Transplant 2020; 29:963689720920830. [PMID: 32393064 PMCID: PMC7586256 DOI: 10.1177/0963689720920830] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Cardiovascular diseases are the leading cause of mortality and morbidity worldwide and account for more than 17.9 million deaths (World Health Organization report). Hypertension and aging are two major risk factors for the development of cardiac structural and functional abnormalities. Hypertension, or elevated blood pressure, if left untreated can result in myocardial hypertrophy leading to heart failure (HF). Left ventricular hypertrophy consequent to pressure overload is recognized as the most important predictor of congestive HF and sudden death. The pathological changes occurring during hypertensive heart disease are very complex and involve many cellular and molecular alterations. In contrast, the cardiac changes that occur with aging are a slow but life-long process and involve all of the structural components in the heart and vasculature. However, these structural changes in the cardiovascular system lead to alterations in overall cardiac physiology and function. The pace at which these pathophysiological changes occur varies between individuals owing to many genetic and environmental risk factors. This review highlights the molecular mechanisms of cardiac structural and functional alterations associated with hypertension and aging.
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Affiliation(s)
- Sherin Saheera
- Department of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, USA
| | - Prasanna Krishnamurthy
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, USA
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Zacharias T, Flouda K, Jepps TA, Gammelgaard B, Schiesser CH, Davies MJ. Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings. Biochem Pharmacol 2020; 173:113631. [DOI: 10.1016/j.bcp.2019.113631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 09/03/2019] [Indexed: 12/17/2022]
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Ali AT, Guidozzi F. Midlife women's health consequences associated with polycystic ovary syndrome. Climacteric 2019; 23:116-122. [PMID: 31657237 DOI: 10.1080/13697137.2019.1679111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common female endocrinopathies. Its symptoms may appear as early as adolescence and may include irregular menstrual periods, amenorrhea, hirsutism and obesity. Regardless of their phenotypic appearance, women with PCOS are metabolically obese. PCOS is associated with metabolic syndrome, type 2 diabetes, depression, cardiovascular disease and gynecological cancers. The metabolic disorders in obese women with PCOS are invariably due to insulin resistance, while inflammation, oxidative stress and possible interaction with environmental factors are among the features linking women with PCOS alone to metabolic disorders. The current review aims to highlight the relationship between PCOS and midlife women's health complications.
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Affiliation(s)
- A T Ali
- Department of Chemical Pathology, NHLS, Tygerberg Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - F Guidozzi
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Amen OM, Sarker SD, Ghildyal R, Arya A. Endoplasmic Reticulum Stress Activates Unfolded Protein Response Signaling and Mediates Inflammation, Obesity, and Cardiac Dysfunction: Therapeutic and Molecular Approach. Front Pharmacol 2019; 10:977. [PMID: 31551782 PMCID: PMC6747043 DOI: 10.3389/fphar.2019.00977] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 07/31/2019] [Indexed: 12/25/2022] Open
Abstract
Obesity has been implicated as a risk factor for insulin resistance and cardiovascular diseases (CVDs). Although the association between obesity and CVD is a well-established phenomenon, the precise mechanisms remain incompletely understood. This has led to a relative paucity of therapeutic measures for the prevention and treatment of CVD and associated metabolic disorders. Recent studies have shed light on the pivotal role of prolonged endoplasmic reticulum stress (ERS)-initiated activation of the unfolded protein response (UPR), the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS). In this aspect, potential ways of attenuating ERS-initiated UPR signaling seem a promising avenue for therapeutic interventions. We review intersecting role of obesity-induced ERS, chronic inflammation, insulin resistance, and oxidative stress in the discovery of targeted therapy. Moreover, this review highlights the current progress and strategies on therapeutics being explored in preclinical and clinical research to modulate ERS and UPR signaling.
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Affiliation(s)
- Omar Mohammed Amen
- School of Bioscience, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
| | - Satyajit D. Sarker
- Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Reena Ghildyal
- Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Canberra, Australia
| | - Aditya Arya
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
- Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
- Malaysian Institute of Pharmaceuticals and Nutraceuticals, Bukit Gambir, Malaysia
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Redox Balance Correlates with Nutritional Status among Patients with End-Stage Renal Disease Treated with Maintenance Hemodialysis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:6309465. [PMID: 31583040 PMCID: PMC6748197 DOI: 10.1155/2019/6309465] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 07/16/2019] [Accepted: 08/16/2019] [Indexed: 12/12/2022]
Abstract
Over 50% of end-stage renal disease (ESRD) patients die of cardiovascular disease. ESRD patients treated with maintenance hemodialysis are repeatedly exposed to oxidative stress. The aim of the study was to find the relationship between lifestyle factors, nutritional status, calcium-phosphate metabolism, and selected redox parameters such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), uric acid (UA), and total antioxidant capacity expressed as ferric reducing antioxidant power (FRAP). The study included 97 ESRD hemodialysis patients and 42 controls with no renal disease. Patients were asked to complete a questionnaire which gathered information on their physical activity, hours of sleep, smoking, and frequency of fruit and vegetable intake; the blood samples were then drawn before the midweek dialysis session. The ESRD patients had lower levels of GR, GPx, and SOD activity, a lower level of FRAP, and a higher UA concentration than the control group. The FRAP value decreased with age (ρ = −0.32, p = 0.001); smokers had a significantly lower SOD activity in comparison to nonsmokers (p = 0.03). In the ESRD patients, FRAP and UA correlated with both albumin (ρ = 0.26, p = 0.011; ρ = 0.41, p = 0.006, respectively) and prealbumin (ρ = 0.34, p ≤ 0.001; ρ = 0.28, p = 0.006, respectively), whereas UA, GR, GPx, and SOD correlated with calcium, UA, GR, and GPx with phosphate level. Based on the findings, there are weak associations between nutritional status and selected redox parameters in hemodialyzed patients. Further studies are needed to establish if diet modifications and adequate nutritional status can positively impact the antioxidant capacity in this group of patients.
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Lee CH, Shin HW, Shin DG. Impact of Oxidative Stress on Long-Term Heart Rate Variability: Linear Versus Non-Linear Heart Rate Dynamics. Heart Lung Circ 2019; 29:1164-1173. [PMID: 31495726 DOI: 10.1016/j.hlc.2019.06.726] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 05/29/2019] [Accepted: 06/18/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Heart rate variability (HRV) is a widely used non-invasive and quantitative marker of cardiac autonomic control. Elevated oxidative stress (OS) and reduced HRV have been proven in specific disease subsets. However, the impact of OS on the long-term heart rate dynamics of both conventional linear and non-linear origin in the general population is not known. METHODS The 24-hour ambulatory electrocardiogram recordings and plasma 8-iso-prostaglandin F2α (8-iso-PGF2α) levels as an OS marker were acquired simultaneously in 71 consecutive patients. The conventional time and frequency domain HRV parameters and non-linear parameters were measured. RESULTS The 8-iso-PGF2α is a significant determinant of most long-term conventional time and frequency domain HRV parameters and standard deviation (SD1, perpendicular to the line of identity; SD2, along the line of identity) descriptors from Poincaré plot analysis, but not of non-linear complexity and fractal parameters. Patients with a high OS burden had lower absolute low-frequency and high-frequency powers during both the night and morning periods, with a significant decrease in high-frequency power in the morning. CONCLUSIONS Oxidative stress is one of the significant determinants of the HRV. The severity of OS is reflected in the conventional time and frequency domain HRV parameters, but not in the non-linear measurements.
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Affiliation(s)
- Chan-Hee Lee
- Division of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Hyun-Woo Shin
- School of Biotechnology, Yeungnam University, Daegu, Republic of Korea
| | - Dong-Gu Shin
- Division of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea.
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Duan J, Du J, Jin R, Zhu W, Liu L, Yang L, Li M, Gong Q, Song B, Anderson JM, Ai H. Iron oxide nanoparticles promote vascular endothelial cells survival from oxidative stress by enhancement of autophagy. Regen Biomater 2019; 6:221-229. [PMID: 31404327 PMCID: PMC6683953 DOI: 10.1093/rb/rbz024] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 05/15/2019] [Accepted: 05/28/2019] [Indexed: 02/05/2023] Open
Abstract
Dextran-coated superparamagnetic iron oxide nanoparticles (Dex-SPIONs) are excellent magnetic resonance imaging contrast agents for disease diagnosis and therapy. They can be delivered to target tissues mainly though vascular endothelium cells, which are major targets of oxidative stress. In cardiovascular cells, autophagy serves primarily on a pro-survival approach that protects the cells from oxidative stress even some autophagy inducers have been developed for adjuvant therapy of cardiovascular disorders. Our study demonstrated that the nanoparticles could be taken up by human umbilical vein endothelial cells (HUVECs) without causing obvious cytotoxicity but triggering autophagy. Furthermore, our results revealed that Dex-SPIONs could enhance HUVECs survival and reverse the reduction of nitric oxide secretion under the condition of H2O2 damage. However, these effects could be diminished by the autophagy inhibitor. In particular, we discovered that Dex-SPIONs evoked autophagy in HUVECs by reducing the phosphorylation of PRAS40, an upstream regulator of autophagy initiation. These results suggested that Dex-SPIONs functions as an autophagic-related antioxidant in HUVECs which may be utilized as an adjuvant therapy to cardiovascular disease associated with oxidative stress.
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Affiliation(s)
- Jimei Duan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
| | - Jiuju Du
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
| | - Rongrong Jin
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
- Correspondence address. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, P.R. China. Tel: +86-28-8541-3991; Fax: +86-28-8541-3991; E-mail: (R.J.); (H.A.)
| | - Wencheng Zhu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
- Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, P.R. China
| | - Li Liu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
| | - Li Yang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
| | - Mengye Li
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
| | - Qiyong Gong
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - James M Anderson
- Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
- Department of Macromolecular Science, Case Western Reserve University, Cleveland, OH, USA
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Hua Ai
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P.R. China
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, P.R. China
- Correspondence address. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, P.R. China. Tel: +86-28-8541-3991; Fax: +86-28-8541-3991; E-mail: (R.J.); (H.A.)
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Toledo C, Andrade DC, Díaz HS, Inestrosa NC, Del Rio R. Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment. Mol Neurobiol 2019; 56:8035-8051. [PMID: 31165973 DOI: 10.1007/s12035-019-01655-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 05/20/2019] [Indexed: 01/01/2023]
Abstract
Heart failure (HF) is a major public health issue affecting more than 26 million people worldwide. HF is the most common cardiovascular disease in elder population; and it is associated with neurocognitive function decline, which represent underlying brain pathology diminishing learning and memory faculties. Both HF and neurocognitive impairment are associated with recurrent hospitalization episodes and increased mortality rate in older people, but particularly when they occur simultaneously. Overall, the published studies seem to confirm that HF patients display functional impairments relating to attention, memory, concentration, learning, and executive functioning compared with age-matched controls. However, little is known about the molecular mechanisms underpinning neurocognitive decline in HF. The present review round step recent evidence related to the possible molecular mechanism involved in the establishment of neurocognitive disorders during HF. We will make a special focus on cerebral ischemia, neuroinflammation and oxidative stress, Wnt signaling, and mitochondrial DNA alterations as possible mechanisms associated with cognitive decline in HF. Also, we provide an integrative mechanism linking pathophysiological hallmarks of altered cardiorespiratory control and the development of cognitive dysfunction in HF patients. Graphical Abstract Main molecular mechanisms involved in the establishment of cognitive impairment during heart failure. Heart failure is characterized by chronic activation of brain areas responsible for increasing cardiac sympathetic load. In addition, HF patients also show neurocognitive impairment, suggesting that the overall mechanisms that underpin cardiac sympathoexcitation may be related to the development of cognitive disorders in HF. In low cardiac output, HF cerebral infarction due to cardiac mural emboli and cerebral ischemia due to chronic or intermittent cerebral hypoperfusion has been described as a major mechanism related to the development of CI. In addition, while acute norepinephrine (NE) release may be relevant to induce neural plasticity in the hippocampus, chronic or tonic release of NE may exert the opposite effects due to desensitization of the adrenergic signaling pathway due to receptor internalization. Enhanced chemoreflex drive is a major source of sympathoexcitation in HF, and this phenomenon elevates brain ROS levels and induces neuroinflammation through breathing instability. Importantly, both oxidative stress and neuroinflammation can induce mitochondrial dysfunction and vice versa. Then, this ROS inflammatory pathway may propagate within the brain and potentially contribute to the development of cognitive impairment in HF through the activation/inhibition of key molecular pathways involved in neurocognitive decline such as the Wnt signaling pathway.
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Affiliation(s)
- C Toledo
- Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile.,Center for Aging and Regeneration (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile
| | - D C Andrade
- Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile.,Centro de investigación en fisiología del ejercicio, Universidad Mayor, Santiago, Chile
| | - H S Díaz
- Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - N C Inestrosa
- Center for Aging and Regeneration (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.,Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile
| | - R Del Rio
- Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile. .,Center for Aging and Regeneration (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile. .,Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile.
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Dos Santos da Rocha P, de Araújo Boleti AP, do Carmo Vieira M, Carollo CA, da Silva DB, Estevinho LM, Dos Santos EL, de Picoli Souza K. Microbiological quality, chemical profile as well as antioxidant and antidiabetic activities of Schinus terebinthifolius Raddi. Comp Biochem Physiol C Toxicol Pharmacol 2019; 220:36-46. [PMID: 30797984 DOI: 10.1016/j.cbpc.2019.02.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 02/14/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023]
Abstract
Schinus terebinthifolius Raddi, commonly known as Brazilian peppertree, is a plant species widely used in Brazilian traditional medicine for various purposes. The objective of this study was to assess the microbiological quality, safety, chemical profile as well as antioxidant and antidiabetic potentials of different parts of S. terebinthifolius. Microbiological analysis of the methanolic extracts of the roots (MESR), stem bark (MESB) and leaves (MESL) of S. terebinthifolius showed no microbial growth. The concentrations of phenolic compounds, phenolic acids and flavonoids were determined by spectrophotometry. The phenolic compounds of the MESL were identified by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS). The antioxidant activities of the extracts were analyzed by 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS+), fluorescence recovery after photobleaching (FRAP), reducing power, β-carotene bleaching and malondialdehyde (MDA) assays in human erythrocytes. The antidiabetic properties of the extracts were demonstrated in vitro by their inhibition of the α-glucosidase enzyme and their anti-glycation activity via fructose and glyoxal. After showing no acute toxicity in vivo, MESL was able to lower postprandial glycemia after glucose overload in normoglycemic mice as well as the water and feed intake, liver weight, glycemia and serum levels of glycated hemoglobin, aspartate transaminase (AST) and alanine transaminase (ALT) in diabetic mice. Overall, S. terebinthifolius extracts showed microbiological safety along with antioxidant and antidiabetic activities, likely mediated by its chemical constituents, such as gallic acid, gallotannins and glycosylated flavonols.
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Affiliation(s)
- Paola Dos Santos da Rocha
- Research group on Biotechnology and Bioprospecting Applied to Metabolism, Federal University of Grande Dourados, Rodovia Dourados Itahum, Km 12, 79804-970 Dourados, MS, Brazil
| | - Ana Paula de Araújo Boleti
- Research group on Biotechnology and Bioprospecting Applied to Metabolism, Federal University of Grande Dourados, Rodovia Dourados Itahum, Km 12, 79804-970 Dourados, MS, Brazil
| | - Maria do Carmo Vieira
- Agricultural Sciences, Federal University of Grande Dourados, Rodovia Dourados-Itahum, Km 12, Brazil
| | - Carlos Alexandre Carollo
- Laboratory of Natural Products and Mass Spectrometry, Federal University of Mato Grosso do Sul, Cidade Universitária, 79070-900 Campo Grande, MS, Brazil
| | - Denise Brentan da Silva
- Laboratory of Natural Products and Mass Spectrometry, Federal University of Mato Grosso do Sul, Cidade Universitária, 79070-900 Campo Grande, MS, Brazil
| | - Leticia Miranda Estevinho
- Polytechnic Institute of Bragança, Agricultural College of Bragança, Campus Santa Apolónia, 5301-855 Bragança, Portugal
| | - Edson Lucas Dos Santos
- Research group on Biotechnology and Bioprospecting Applied to Metabolism, Federal University of Grande Dourados, Rodovia Dourados Itahum, Km 12, 79804-970 Dourados, MS, Brazil
| | - Kely de Picoli Souza
- Research group on Biotechnology and Bioprospecting Applied to Metabolism, Federal University of Grande Dourados, Rodovia Dourados Itahum, Km 12, 79804-970 Dourados, MS, Brazil.
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Hort J, Vališ M, Kuča K, Angelucci F. Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits. Int J Mol Sci 2019; 20:E2405. [PMID: 31096580 PMCID: PMC6566630 DOI: 10.3390/ijms20102405] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 05/06/2019] [Accepted: 05/13/2019] [Indexed: 12/16/2022] Open
Abstract
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.
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Affiliation(s)
- Jakub Hort
- Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic.
- International Clinical Research Centre, St. Anne's University Hospital, 656 91 Brno, Czech Republic.
| | - Martin Vališ
- Department of Neurology, University Hospital Hradec Králové, Charles University in Prague, Faculty of Medicine in Hradec Králové, Sokolská Street 581, 500 05 Hradec Králové, Czech Republic.
| | - Kamil Kuča
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, 500 05 Hradec Kralove, Czech Republic.
| | - Francesco Angelucci
- Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 150 06 Prague, Czech Republic.
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Manu TM, Anand T, Pandareesh MD, Kumar PB, Khanum F. Terminalia arjuna extract and arjunic acid mitigate cobalt chloride-induced hypoxia stress-mediated apoptosis in H9c2 cells. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:1107-1119. [PMID: 31069430 DOI: 10.1007/s00210-019-01654-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 04/11/2019] [Indexed: 12/11/2022]
Abstract
Arjunic acid (AA) is one of the major active component of Terminalia arjuna known for its health benefits. In the present study, we evaluated cardioprotective potential of Terminalia arjuna extract (TAE) and AA against cobalt chloride (CoCl2)-induced hypoxia damage and apoptosis in rat cardiomyocytes. TAE (50 μg/ml) and AA (8 μg/ml) significantly (p < 0.001) protected H9c2 cells as evidenced by cell viability assays against CoCl2 (1.2 mM)-induced cytotoxicity. TAE and AA pretreatments protected the cells from oxidative damage by decreasing the generation of free radicals (ROS, hydroperoxide, and nitrite levels). TAE and AA pretreatments retained mitochondrial membrane potential by alleviating the rate of lipid peroxidation induced by CoCl2 treatment. TAE and AA pretreatments elevated antioxidant status including phase II antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and total glutathione levels against CoCl2-induced oxidative stress. Further immunoblotting studies confirmed anti-apoptotic effects of TAE and AA by alleviating the phosphorylation of JNK and c-jun and also by regulating protein expression levels of Bcl2, Bax, caspase 3, heat shock protein-70, and inducible nitric oxide synthase. Overall, our results suggest that both the extract and the active component exhibit antioxidant and anti-apoptotic defense against CoCl2-induced hypoxic injury.
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Affiliation(s)
- T Mohan Manu
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, 570011, India
| | - T Anand
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, 570011, India.
| | - M D Pandareesh
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, 570011, India
| | - P Bhuvanesh Kumar
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, 570011, India
| | - Farhath Khanum
- Nutrition, Biochemistry and Toxicology Division, Defence Food Research Laboratory, Mysuru, 570011, India
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Ayoub L, Hassan F, Hamid S, Abdelhamid Z, Souad A. Phytochemical screening, antioxidant activity and inhibitory potential of Ficus carica and Olea europaea leaves. Bioinformation 2019; 15:226-232. [PMID: 31354199 PMCID: PMC6637399 DOI: 10.6026/97320630015226] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 10/27/2018] [Accepted: 10/28/2018] [Indexed: 01/06/2023] Open
Abstract
It is our interest to screen Oela europaea L and Ficus carica L leaf extract for total phenolic, flavonoid contents and to evaluate their free radical scavenging and Ferric reducing power (FRAP) using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Data shows that Olea europaea and Ficus carica have strong antioxidant potency to scavenge free radical at an optimal phenolic and flavonoid concentration. Results further suggest a strong correlation between antioxidant activities, phenolic and flavonoid contents. Thus, the screening of Ficus carica and Olea europaea leaf extracts for potential antioxidants as source of drugs for several diseases especially oxidative stress and cancers is illustrated.
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Affiliation(s)
- Lahmadi Ayoub
- Laboratory of Biochemistry, Environment and Agri-Food (URAC 36) - Faculty of Sciences and Techniques - Mohammedia, Hassan II
university Casablanca- Morocco
| | - Filali Hassan
- Laboratory of Biochemistry, Environment and Agri-Food (URAC 36) - Faculty of Sciences and Techniques - Mohammedia, Hassan II
university Casablanca- Morocco
| | - Samaki Hamid
- National Institute of Social Action (INAS), Tangier, Morocco
| | - Zaid Abdelhamid
- Environment and Health. Faculty of Sciences, University Moulay Ismail, Meknes Morocco
| | - Aboudkhil Souad
- Laboratory of Biochemistry, Environment and Agri-Food (URAC 36) - Faculty of Sciences and Techniques - Mohammedia, Hassan II
university Casablanca- Morocco
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Long Noncoding RNAs in the Regulation of Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:1318795. [PMID: 30911342 PMCID: PMC6398004 DOI: 10.1155/2019/1318795] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 11/29/2018] [Accepted: 12/18/2018] [Indexed: 12/25/2022]
Abstract
Oxidative stress takes responsibility for various diseases, such as chronic obstructive pulmonary disease (COPD), Alzheimer's disease (AD), and cardiovascular disease; nevertheless, there is still a lack of specific biomarkers for the guidance of diagnosis and treatment of oxidative stress-related diseases. In recent years, growing studies have documented that oxidative stress has crucial correlations with long noncoding RNAs (lncRNAs), which have been identified as important transcriptions involving the process of oxidative stress, inflammation, etc. and been regarded as the potential specific biomarkers. In this paper, we review links between oxidative stress and lncRNAs, highlight lncRNAs that refer to oxidative stress, and conclude that lncRNAs have played a negative or positive role in the oxidation/antioxidant system, which may be helpful for the further investigation of specific biomarkers of oxidative stress-related diseases.
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Adult Cardiac Stem Cell Aging: A Reversible Stochastic Phenomenon? OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:5813147. [PMID: 30881594 PMCID: PMC6383393 DOI: 10.1155/2019/5813147] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Accepted: 11/08/2018] [Indexed: 12/17/2022]
Abstract
Aging is by far the dominant risk factor for the development of cardiovascular diseases, whose prevalence dramatically increases with increasing age reaching epidemic proportions. In the elderly, pathologic cellular and molecular changes in cardiac tissue homeostasis and response to injury result in progressive deteriorations in the structure and function of the heart. Although the phenotypes of cardiac aging have been the subject of intense study, the recent discovery that cardiac homeostasis during mammalian lifespan is maintained and regulated by regenerative events associated with endogenous cardiac stem cell (CSC) activation has produced a crucial reconsideration of the biology of the adult and aged mammalian myocardium. The classical notion of the adult heart as a static organ, in terms of cell turnover and renewal, has now been replaced by a dynamic model in which cardiac cells continuously die and are then replaced by CSC progeny differentiation. However, CSCs are not immortal. They undergo cellular senescence characterized by increased ROS production and oxidative stress and loss of telomere/telomerase integrity in response to a variety of physiological and pathological demands with aging. Nevertheless, the old myocardium preserves an endogenous functionally competent CSC cohort which appears to be resistant to the senescent phenotype occurring with aging. The latter envisions the phenomenon of CSC ageing as a result of a stochastic and therefore reversible cell autonomous process. However, CSC aging could be a programmed cell cycle-dependent process, which affects all or most of the endogenous CSC population. The latter would infer that the loss of CSC regenerative capacity with aging is an inevitable phenomenon that cannot be rescued by stimulating their growth, which would only speed their progressive exhaustion. The resolution of these two biological views will be crucial to design and develop effective CSC-based interventions to counteract cardiac aging not only improving health span of the elderly but also extending lifespan by delaying cardiovascular disease-related deaths.
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