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.