title: Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats.
abstract: Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
authors.forename: Surinder Kumar
authors.initials: SK
authors.lastname: Yogeeta
authors.forename: Hanumantha Rao Balaji
authors.initials: HR
authors.lastname: Raghavendran
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Gnanapragasam
authors.forename: Rajakannu
authors.initials: R
authors.lastname: Subhashini
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Devaki
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D003580:Cytochromes / Q000378:metabolism; D004357:Drug Synergism; D005978:Glutathione / Q000032:analysis; D006331:Heart Diseases / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007545:Isoproterenol / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000032:analysis; D008297:Male; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000318:Adrenergic beta-Agonists; D003373:Coumaric Acids; D003580:Cytochromes; D008054:Lipid Peroxides; C004999:ferulic acid; D005978:Glutathione; D007545:Isoproterenol; D001205:Ascorbic Acid