Ameliorative prospective of alpha-mangostin, a xanthone derivative from Garcinia mangostana against beta-adrenergic cathecolamine-induced myocardial toxicity and anomalous cardiac TNF-alpha and COX-2 expressions in rats.
Altered membrane integrity and inflammation play a key role in cardiovascular damage. We investigated the salubrious effect of exogenously administered alpha-mangostin against beta-adrenergic cathecolamine-induced cardiovascular toxicity with special reference to membrane ATPases, lysosomal hydrolases and inflammatory mediators TNF-alpha and Cyclooxygenase-2 (COX-2) expressions in albino rats. Induction of rats with isoproterenol (150mg/kg body wt, i.p.) for 2 days resulted in a significant increase in the activities of serum and cardiac lysosomal hydrolases (beta-d-glucuronidase, beta-d-galactosidase, beta-d-N-acetylglucosaminidase, acid phosphatase and cathepsin-D). A significant increase in cardiac levels of sodium, calcium with a decrease in the level of potassium paralleled by abnormal activities of membrane-bound phosphatases (Na(+)-K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase) were observed in the heart of ISO-administered rats. Cardiac TNF-alpha and COX-2 expressions were assessed by Western blotting. Cardiac TNF-alpha and COX-2 expressions were significantly elevated in ISO-intoxicated rats. Pre-co-treatment with alpha-mangostin (200mg/kg body wt.) orally for 8 days significantly attenuated these abnormalities and restored the levels to near normalcy when compared to ISO intoxicated group of rats. In conclusion, alpha-mangostin preserves the myocardial membrane integrity and extenuates anomalous TNF-alpha and COX-2 expressions by mitigating ISO-induced oxidative stress and cellular damage effectively. Restoration of cellular normalcy accredits the cytoprotective role of alpha-mangostin.
Sampath
Pandima Devi
PD
Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, India.
Vijayaragavan
Kannan
K
D000318:Adrenergic beta-Agonists / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects*; D029762:Garcinia mangostana / Q000737:chemistry; D006321:Heart / Q000187:drug effects; D006867:Hydrolases / Q000032:analysis / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects*; D044004:Xanthones / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; D051546:Cyclooxygenase 2; D006867:Hydrolases; D007545:Isoproterenol; C021053:mangostin