Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis

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• 作者：Xiao Sun ; Rong-chang Chen ; Zhi-hong Yang ; Gui-bo Sun ; Min Wang ; Xiao-jun Ma ; Li-juan Yang ; Xiao-bo Sun
• 关键词：DCM ; diabetic cardiomyopathy ; ROS ; reactive oxygen species ; STZ ; streptozotocin ; Ang II ; angiotensin II ; LVVd ; LV end-diastolic volume ; LVVs ; LV end-systolic volume ; FS ; fractional shortening ; EF ; ejection fraction ; LDH ; lactate dehydrogenase ; CK-MB ; creatinine kinase-MB isoenzyme ; AST ; aspartate aminotransferase ; MDA ; malondialdehyde ; SOD ; superoxide dismutase ; CAT ; catalase ; GSH-Px ; glutathione peroxidase ; AT1 ; angiotensin receptor 1 ; 螖唯m ; mitochondrial membrane potential ; RAS ; rennin-angiot
• 刊名：Food and Chemical Toxicology
• 出版年：January, 2014
• 年：2014
• 卷：63
• 期：Complete
• 页码：221-232
• 全文大小：3701 K

文摘

Diabetic cardiomyopathy has been increasingly recognized as an important cause of heart failure in diabetic patients. Excessive oxidative stress has been suggested to play a critical role in the development of diabetic cardiomyopathy. The objective of this study was to investigate the potential protective effects and mechanisms of taxifolin on cardiac function of streptozotocin-induced diabetic mice and on hyperglycemia-induced apoptosis of H9c2 cardiac myoblasts. In vivo study revealed that taxifolin improved diastolic dysfunction, ameliorated myocardium structure abnormality, inhibited myocyte apoptosis and enhanced endogenous antioxidant enzymes activities. Interestingly, taxifolin reduced angiotensin II level in myocardium, inhibited NADPH oxidase activity, and increased JAK/STAT3 activation. In vitro investigation demonstrated that taxifolin inhibited 33 mM glucoseinduced H9c2 cells apoptosis by decreasing intracellular ROS level. It also inhibited caspase-3 and caspase-9 activation, restored mitochondrial membrane potential, and regulated the expression of proteins related to the intrinsic pathway of apoptosis, thus inhibiting the release of cytochrome c from mitochondria into the cytoplasm. In conclusion, taxifolin exerted cardioprotective effects against diabetic cardiomyopathy by inhibiting oxidative stress and cardiac myocyte apoptosis and might be a potential agent in the treatment of diabetic cardiomyopathy.