Hesperidin Extracted from Citrus reticulata Blanco Protects Cardiac Mitochondria Against Hypoxia/Reoxygenation Injury
Main Article Content
Abstract
This study was conducted to evaluate the protective effect of Hesperdin (Hes) extracted from Citrus reticulata Blanco on cardiac mitochondria in hypoxia/reoxygenation (HR) injury in vitro. Methods: H9C2 cardiomyocytes were cultured under normal (control), HR, and treatment conditions. The reactive oxygen species and calcium levels in experimental groups were analyzed by using suitable fluorescence kits. Results: The obtained results showed that the addition of Hes at dose of 0,01562 mg/mL sharply decreased the mitochondrial oxidative stress of H9C2 cells under HR conditions. In particular, Hes showed the remarkable efficiency in maintaing cellular calcium levels. In HR-exposed H9C2 cell group, the hydrogen peroxide and superoxide levels were highly increased compared to those in control group (1,54±0,06 and 1,74±0,38, p<0,05). HR also strongly induced the elevation of cytosolic Ca²⁺ and mitochondial Ca²⁺ of H9C2 cardiomyocytes with the values were 1,96±0,05% and 1,62±0,33 (ratio to control, p<0,05), respectively. Interestingly, post-hypoxic supplementation of Hes effectivelly abolished the negative incresement of these indicators with the lower levels of reactive oxygen species and the better modulation of Ca²⁺ homeostasis. Conclusion: The present results are pilot data on the effects of Hes in protecting cardiac mitochondria against HR injury.
Keywords:
H9C2, Cardiolipin, Mitochondrial membrane potential.
References
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2. E. Murphy and C. Steenbergen, Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury. Physiological Reviews,Vol. 88, No. 2, 2008, p. 581-609, https://doi.org/10.1152/physrev.00024.2007.
3. H.t.m.h.V. Nam, Đại hội tim mạch toàn quốc lần thứ 14. http://daihoi14.vnha.org.vn/,Vol., No., 2015.
4. V.T. Thu, et al., NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter. Cardiovasc Res,Vol. 94, No. 2, 2012, p. 342-350, https://doi.org/10.1093/cvr/cvs122.
5. A.K.S. Camara, M. Bienengraeber, and D.F. Stowe, Mitochondrial Approaches to Protect Against Cardiac Ischemia and Reperfusion Injury. Front Physiol,Vol. 2, No., 2011, https://doi.org/10.3389/fphys.2011.00013.
6. D.J. Hausenloy and D.M. Yellon, Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest,Vol. 123, No. 1, 2013, p. 92-100, 10.1172/jci62874.
7. T. Kalogeris, et al., Ischemia/Reperfusion. Comprehensive Physiology,Vol. 7, No. 1, 2016, p. 113-170, https://doi.org/10.1002/cphy.c160006.
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9. Q. Chen, et al., Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion. Am J Physiol Cell Physiol,Vol. 292, No. 1, 2007, p. C137-147, https://doi.org/10.1152/ajpcell.00270.2006.
10. T.A. Ajith and T.G. Jayakumar, Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases. World J Cardiol,Vol. 6, No. 10, 2014, p. 1091-9, https://doi.org/10.4330/wjc.v6.i10.1091.
11. P.G.J. Walters AM, Brookes PS, Mitochondria as a drug target in ischemic heart disease and cardiomyopathy. Circ Res,Vol. 111, No. 9, 2012, p. 1222-36, https://doi.org/10.1161/circresaha.112.265660.
12. P.T. Thuong, et al., Dual anti-oxidative effects of fraxetin isolated from Fraxinus rhinchophylla. Biol Pharm Bull,Vol. 32, No. 9, 2009, p. 1527-32, https://doi.org/10.1248/bpb.32.1527.
13. N.T. Hoai, et al., Screening Medicinal Plants in Central Vietnam for Radical Scavenging and Ferrous ion Chelation Activities. Journal of Medicinal Materials,Vol. 20, No. 3, 2015.
14. T.C. Luan, T.T.T. Quynh, and Salihah, Isolation and identification of antioxidant compounds from leaves of moringa oleiferam lam., moringaceae. Y hoc TP. Ho Chi Minh Vol. 18, No. 1, 2014, p. 175-179.
15. T.M. Hung, N.H. Dang, and N.T. Dat, Methanol extract from Vietnamese Caesalpinia sappan induces apoptosis in HeLa cells. Biological Research,Vol. 47, No. 1, 2014, p. 1-5, https://doi.org/10.1186/0717-6287-47-20.
16. Y.O. Agrawal, et al., Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats. PloS one,Vol. 9, No. 11, 2014, p. e111212-e111212, https://doi.org/10.1371/journal.pone.0111212.
17. Y.O. Agrawal, et al., Hesperidin blunts streptozotocin-isoproternol induced myocardial toxicity in rats by altering of PPAR-γ receptor. Chem Biol Interact,Vol. 219, No., 2014, p. 211-20, https://doi.org/10.1016/j.cbi.2014.06.010.
18. P. Selvaraj and K.V. Pugalendi, Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats. Redox Rep,Vol. 15, No. 5, 2010, p. 217-23, https://doi.org/10.1179/135100010x12826446921509.
19. X. Li, et al., Short-Term Hesperidin Pretreatment Attenuates Rat Myocardial Ischemia/Reperfusion Injury by Inhibiting High Mobility Group Box 1 Protein Expression via the PI3K/Akt Pathway. Cellular Physiology and Biochemistry,Vol. 39, No. 5, 2016, p. 1850-1862, https://doi.org/10.1159/000447884.
20. N.T.H. Yen, et al., Evaluating the Protective Effects if Hespiridin on H9C2 Cells Against Hypoxia/Reoxygenation Injury In Vitro. BÁO CÁO KHOA HỌC VỀ NGHIÊN CỨU VÀ GIẢNG DẠY SINH HỌC Ở VIỆT NAM - HỘI NGHỊ KHOA HỌC QUỐC GIA LẦN THỨ 4,Vol., No., 2020, p. 630-537, https://doi.org/10.15625/vap.2020.00078.
21. V.T. Thu, N.T.H. Yen, and N.T.H. Ly, Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage. Journal of Analytical Methods in Chemistry,Vol. 2021, No., 2021, p. 1857464, https://doi.org/10.1155/2021/1857464.
22. R.B. Martín T., Villaescusa L., Fernández L., Díaz A. M., Polyphenolic compounds from pericarps of Myrtus communis. Pharmaceutical Biology,Vol. 37(1), No., p. 28-31, https://doi.org/10.1076/phbi.37.1.28.6327.
23. Y. Liao, et al., Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death. Protein & cell,Vol. 6, No. 6, 2015, p. 434-442, https://doi.org/10.1007/s13238-015-0144-6.
24. J.L. Groskreutz, S.F. Bronk, and G.J. Gores, Ruthenium red delays the onset of cell death during oxidative stress of rat hepatocytes. Gastroenterology,Vol. 102, No. 3, 1992, p. 1030-1038, https://doi.org/10.1016/0016-5085(92)90193-3.
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