Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana

Drug Chem Toxicol. 2009;32(4):344-52. doi: 10.1080/01480540903159210.

Abstract

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.

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Free Radical Scavengers / therapeutic use
  • Garcinia mangostana / chemistry*
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / prevention & control*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Nitric Oxide Synthase Type III / metabolism*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Protein Kinase Inhibitors
  • Rats
  • Rats, Wistar
  • Xanthones*

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Plant Extracts
  • Protein Kinase Inhibitors
  • Xanthones
  • Nitric Oxide Synthase Type III
  • mangostin