Devika P T, Stanely Mainzen Prince P
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.
Pharmacol Res. 2008 May;57(5):351-7. doi: 10.1016/j.phrs.2008.03.008. Epub 2008 Mar 26.
Altered mitochondrial function and free radical-mediated tissue damage have been suggested as important pathological events in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of (-)epigallocatechin-gallate (EGCG) on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Rats were pretreated with EGCG (30 mg/kg) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100mg/kg) was subcutaneously injected to rats at intervals of 24h for 2 days. ISO-induced rats showed significant increase in mitochondrial lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in mitochondrial antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and reduced glutathione). Also, significantly decreased activities of tricarboxylic acid cycle enzymes such as isocitrate, succinate, malate and alpha-ketoglutarate dehydrogenases and respiratory chain marker enzymes such as NADH-dehydrogenase and cytochrome-c-oxidase were observed in mitochondrial heart of myocardial infarcted rats. Prior treatment with EGCG (30mg/kg body weight) significantly prevented these alterations and restored normal mitochondrial function. Transmission electron microscopic findings also correlated with these biochemical parameters. In vitro studies on the effect of EGCG on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)), superoxide anion (O(-)), and hydroxyl (OH) radicals also confirmed the free radical scavenging and antioxidant activity of EGCG. Thus, the observed effects are due to the free radical scavenging and antioxidant potential of EGCG. Thus, this study confirmed the preventive effect of EGCG on isoproterenol-induced mitochondrial damage in experimentally induced myocardial infarction in Wistar rats.
线粒体功能改变和自由基介导的组织损伤被认为是异丙肾上腺素（ISO）诱导的心脏毒性中的重要病理事件。本研究旨在了解（-）表没食子儿茶素-3-没食子酸酯（EGCG）对雄性Wistar大鼠ISO诱导的心脏毒性中线粒体损伤的预防作用。大鼠每天经胃管口服EGCG（30mg/kg）预处理21天。之后，每隔24小时皮下注射ISO（100mg/kg）给大鼠，共注射2天。ISO诱导的大鼠线粒体脂质过氧化产物（硫代巴比妥酸反应性物质和脂质氢过氧化物）显著增加，线粒体抗氧化剂（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶、谷胱甘肽还原酶和还原型谷胱甘肽）显著减少。此外，在心肌梗死大鼠的线粒体心脏中观察到三羧酸循环酶如异柠檬酸、琥珀酸、苹果酸和α-酮戊二酸脱氢酶以及呼吸链标记酶如NADH-脱氢酶和细胞色素c氧化酶的活性显著降低。用EGCG（30mg/kg体重）预先处理可显著预防这些改变并恢复正常的线粒体功能。透射电子显微镜检查结果也与这些生化参数相关。关于EGCG对清除1,1-二苯基-2-苦基肼（DPPH）、2,2'-偶氮二（3-乙基苯并噻唑啉-6-磺酸）（ABTS(+)）、超氧阴离子（O(-)）和羟自由基（OH）的体外研究也证实了EGCG的自由基清除和抗氧化活性。因此，观察到的效果归因于EGCG的自由基清除和抗氧化潜力。因此，本研究证实了EGCG对Wistar大鼠实验性诱导心肌梗死中异丙肾上腺素诱导的线粒体损伤具有预防作用。
