Ameliorative role of rosiglitazone in hyperhomocysteinemia-induced experimental cardiac hypertrophy.

ABSTRACT

The present study has been designed to explore the beneficial effect of rosiglitazone, a peroxisome proliferator activated receptor-gamma agonist, in hyperhomocysteinemia-induced cardiac hypertrophy in rats. The hyperhomocysteinemia was induced in rats by feeding L-methionine (1.7 g/kg per day orally) for 8 weeks. The development of cardiac hypertrophy was assessed by measuring ratio of left ventricular weight to body weight, left ventricular wall thickness, cardiomyocyte diameter, and mean arterial blood pressure. The extent of fibrosis was checked by biochemical and histological assessment of collagen deposition. Moreover, the oxidative stress in heart was measured in terms of an increase in thiobarbituric acid reactive substances, superoxide anion generation, and decrease in reduced glutathione levels. The treatment with rosiglitazone (5 and 10 mg/kg per day orally) started from the first day of administration of L-methionine significantly abolished hyperhomocysteinemia-induced increase in left ventricular weight to body weight ratio, left ventricular wall thickness, cardiomyocyte diameter, collagen deposition, and oxidative stress without affecting serum homocysteine levels in rats. At high dose, rosiglitazone markedly reduced mean arterial blood pressure but at low dose, a significant reduction in mean arterial blood pressure was not observed in hyperhomocysteinemic rats. Hence, our results suggest that rosiglitazone provides benefit in hyperhomocysteinemia-induced cardiac hypertrophy and fibrosis in a dose-dependent manner and its protective action is independent of change in mean arterial blood pressure and serum homocysteine levels in rats.