(-)epigallocatechin-gallate (EGCG) prevents mitochondrial damage in isoproterenol-induced cardiac toxicity in albino Wistar rats:: A transmission electron microscopic and in vitro study

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 (100 mg/kg) was subcutaneously injected to rats at intervals of 24 h 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 clehydrogenases 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 (30 mg/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 center dot), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)), superoxide anion (O center dot-), and hydroxyl (OH center dot) 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 EGCC. Thus, this study confirmed the preventive effect of EGCG on isoproterenol-induced mitochondrial damage in experimentally induced myocardial infarction in Wistar rats. (C) 2008 Elsevier Ltd. All rights reserved.