Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana.
Oxidative stress can play a key role in myocardial necrosis. The present study was designed to investigate the effect of alpha-mangostin (an antioxidant phytonutrient) on mitochondrial dysfunction and endothelial nitric oxide synthase (eNOS) expression during isoproterenol-induced myocardial necrosis in rats. Induction of rats with isoproterenol (ISO) (150 mg/kg body weight, intraperitoneally) 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, and alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, and GSH), mitochondrial cytochromes (b, c, c1, and aa3), and adenosine triphosphate level. A marked elevation in mitochondrial lipid peroxidation was also observed in ISO-intoxicated rats. Pretreatment with alpha-mangostin (200 mg/kg body weight) orally for 8 days significantly attenuated these functional abnormalities and restored normal mitochondrial function, when compared to the ISO-intoxicated group of rats. Cardiac eNOS expression was assessed by Western blot. Cardiac eNOS expression and NO level were significantly suppressed in ISO-intoxicated rats. Pretreatment with alpha-mangostin extenuated ISO-induced diminution of eNOS expression and NO level. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings conclude the ameliorative potential of alpha-mangostin against ISO-induced biochemical and morphological changes in mitochondria, which might be mediated through the NO pathway and by its ability at quenching free radicals.
Sampath
Pandima Devi
PD
Center for Advanced Studies in Botany, University of Madras, Chennai, India.
Kannan
Vijayaragavan
V
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000627:therapeutic use; D029762:Garcinia mangostana / Q000737:chemistry*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D044004:Xanthones
D000975:Antioxidants; D016166:Free Radical Scavengers; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D044004:Xanthones; D052250:Nitric Oxide Synthase Type III; C021053:mangostin