Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats

The potential protective effect of epigallocatechin-3-gallate (EGCG) on type 2 diabetes-induced heart injury was investigated. A rat model of diabetes was achieved by injection of nicotinamide (100 mg/kg, i.p), 20 min before the administration of streptozotocin (55 mg/kg, i.p.). After confirmation of diabetes, EGCG (2 mg/kg, p.o.) was administrated on alternate days for one month. Treatment of diabetic rats with EGCG showed a remarkable reduction in glucose, glycosylated hemoglobin, HOMA-IR and lipid profile levels with an elevation in insulin levels, indicating its antihyperglycemic and antidyslipidemic actions. EGCG treatment also suppressed the increase in the levels of superoxide, 4-hydroxynonenal and protein carbonyl, whereas it increased the content of glutathione and the activities of superoxide dismutase and catalase in heart of diabetic rats, indicating its antioxidant capacity. In addition, EGCG improved heart function of diabetic rats as evidenced by a remarkable reduction in troponin T level and creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities in the serum. Oral administration of EGCG for one month after diabetes induction significantly protected the increase in serum levels of pro-inflammatory cytokines (IL-1 β, IL-6 and TNF-α) and adhesion molecules (ICAM-1 and VCAM-1), suggesting its anti-inflammatory potential. Furthermore, EGCG hampered the mitochondrial apoptotic pathway through increasing Bcl-2 level and decreasing p53, Bax, cytochrome c and caspase-3 and 9 levels in hearts of diabetic rats, indicating its anti-apoptotic action. Diabetic rats treated with EGCG also exhibited decreased level of DNA damage in the myocardium. The histological examinations indicated the cardioprotective effect of EGCG against harmful impact of diabetes. Therefore, these findings suggest that EGCG has a protective effect on the heart affected by type 2 diabetes and recommend it as a complementary supplement for diabetic patients.

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