ABSTRACT
Cardiomyocyte apoptosis in heart failure has been the topic of research in many recent studies. In the present investigation, the potential cardioprotective effect of gymnemic acid phospholipid complex (GPC) on myocardial apoptosis and cardiac function was studied in doxorubicin (DOX; 30 mg/kg/ip/single dose)-induced cardiomyopathy model in rats. Doxorubicin induced cardiomyopathy was evidenced by significant hemodynamic changes (increased systolic, diastolic, mean arterial pressure and heart rate), decreased heart weight to body weight ratio, increase in serum lactate dehydrogenase (LDH) and Ca2+ levels and decrease in myocardial Na+/K+ ATPase levels along with caspase-3 activation. A marked reduction in glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase levels along with increase in the levels of thiobarbituric acids (TBARS) were also observed in rat myocardium. In addition, DNA laddering observed on agarose gel electrophoresis and cardiac histopathology study further supplemented myocardial apoptosis. Pre-treatment with GPC significantly reduced DOX-induced cardiac toxicity, including improvement of hemodynamic variables and heart weight to body weight ratio, decreased serum Ca2+ level and LDH levels, myocardial caspase-3 levels, increased Na+/K+ ATPase levels and decreased myocardial TBARS levels and elevated antioxidant enzymes as compared to pathogenic control group. Further, the anti-apoptotic effect of GPC was verified by prevention of internucleosomal DNA laddering on agarose gel electrophoresis and attenuation of histopathological perturbations by doxorubicin. These observations demonstrate that GPC might serve as a cardioprotective formulation in DOX-induced cardiomyopathy in rats.
ABSTRACT
Methionine (1g/kg, po) administration to pathogenic control rats for 30 days significantly increased the levels of homocysteine, total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) and triglycerides (TGs) and decreased the levels of high density lipoprotein (HDL-C) in serum. Hematological observations of the peripheral blood smears of pathogenic rats fed with methionine also showed crenation of RBCs cell membrane and significant increase in total leukocyte count, differential leukocyte count and platelet counts with significant decrease in the mean hemoglobin levels as compared to vehicle control rats. Administration of atorvastatin (0.2 mg/kg/po) to hyperhomocysteinemic rats significantly decreased the levels of homocysteine, TC, TGs, LDL-C and VLDL-C and increased the levels of HDL-C in serum. The present results provide clear evidence that oral treatment with atorvastatin exhibit homocysteine and lipid lowering activity and also reversal of hematological changes induced by methionine in albino rats.