Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction
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- 作者：Azza I. Othman ; Magda M. Elkomy ; M.A. El-Missiry ; maelmissiry@yahoo.com ; elmissiry@mans.edu.eg ; Mohammed Dardor
- 关键词：Heart ; Polyphenols ; EGCG ; Isoproterenol ; Oxidative stress ; Apoptosis ; Caspases
- 刊名：European Journal of Pharmacology
- 出版年：2017
- 出版时间：5 January 2017
- 年：2017
- 卷：794
- 期：Complete
- 页码：27-36
- 全文大小：1123 K
- 卷排序：794
文摘
(−)Epigallocatechin-gallate (EGCG) is an emerging natural therapy. This study examined the cardioprotective effect of EGCG on isoproterenol-induced myocardial damage and apoptosis and EGCG's role in modulating the expression of apoptotic signaling proteins. Experimental myocardial infarction was induced in albino Westar rats by isoproterenol (ISO) administration (100 mg/kg, s.c.) at an interval of 24 h on the 6th and 7th day. EGCG (15 mg/kg, i.p.) was administered seven days before ISO. EGCG pretreatment significantly showed an anti-lipidemic effect and protected the cell membrane integrity, as shown by the blocking of changes in serum levels of CK-MB, LDH, ALP, ALT and troponin T. EGCG also maintained the redox balance by preventing the inhibition of the activity of SOD and CAT while limiting lipid peroxidation. Pretreatment with EGCG inhibited the stimulation of the pro-inflammatory cytokine, TNF-α, in the serum. In animals treated with EGCG, tissue Bcl-2 expression exceeded the values observed after ISO treatment and down-regulated the expression of pro-apoptotic signaling proteins, including Bax, caspase-9 and 3. This is accompanied by the protection of genomic integrity by inhibiting DNA fragmentation coincident with the down-regulation of P53. In conclusion, EGCG protected against cardiac damage by decreasing apoptosis in myocardium tissue by 1) maintaining the balance of anti-apoptotic / pro-apoptotic signaling proteins in the mitochondrial pathway of cell death, 2) limiting oxidative stress while performing antioxidant and anti-inflammatory effects, and 3) protecting DNA integrity, sustaining cardiac health. Therefore, EGCG is potentially beneficial as an early intervention in cardiac attack.