Anti-apoptotic potential of rosuvastatin pretreatment in murine model of cardiomyopathy

Background: Apoptosis is a key pathologic feature in myocardial infarction and heart failure. Recent evidence suggests that statins may have beneficial effects on cardiovascular outcomes in patients with heart failure. The present study was planned to investigate the anti-apoptotic potential of rosuvastatin pretreatment in doxorubicin-induced cardiomyopathy. Methods: Sixty male Wistar rats were randomly divided into six groups: Group-I (vehicle control group), Group-II (pathological Control group), Group-III (rosuvastatin 0.5 mg/kg), Group IV (rosuvastatin 2 mg/kg), Group-V (rosuvastatin 2 mg/kg per se), and Group-VI (carvedilol 1 mg/kg). Myocardial apoptosis was detected by caspase-3 assay, DNA gel electrophoresis and Na+/K+ ATPase estimation. The animals were evaluated for various biochemical parameters in serum followed by histopathological studies of heart tissue. Results: Doxorubicin treated rats exhibited cardiac dysfunctions as indicated by an increase in systolic, diastolic, mean BP, heart rate and tail blood flow and volume and increased serum LDH, TC, TGs, LDL-C, VLDL-C levels and atherogenic indexes. A marked induction in caspase-3 and Na+-K+ ATPase levels and DNA laddering as revealed by agarose gel electrophoresis was observed in rat myocardium of pathological group. Pretreatment with the test drug, rosuvastatin significantly reduced the increase in hemodynamic parameters, serum LDH, lipid profile and myocardial caspase-3, Na+-K+ ATPase activity as compared to the pathogenic control group. Further, DNA ladder formation was attenuated by rosuvastatin treatment. Histopathological studies further confirm its myocardial salvaging effects. The results were comparable with carvedilol. Conclusions: The study demonstrates the cardioprotective potential of rosuvastatin against doxorubicin-induced myocardial apoptosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.