Rosiglitazone and pioglitazone aggravate doxorubicin-induced cardiomyopathy in Wistar rats

Recently the cardiovascular safety of thiazolidinediones (TZDs) has been questioned. This study was designed to assess the effect of rosiglitazone (ROSI 5 mg/kg p.o.) and pioglitazone (PIO 10 mg/kg p.o.) on doxorubicin (DOX 15 mg/kg i.p. single dose) induced cardiomyopathy in Wistar rats. DOX (15 mg/kg i.p. single dose) induced cardiomyopathy was evidenced by a significant (p < 0.001) increase in serum lactate dehydrogenase (LDH), cholesterol profile, thiobarbituric acid reactive substance (TBARS), catalase (CAT) levels and a significant (p < 0.001) decrease in glutathione and superoxide dismutase levels followed by histopathological and transmission electron microscopic changes. Rosiglitazone (5 mg/kg p.o.) and pioglitazone (10 mg/kg p.o.) were administered for 14 days and doxorubicin (15 mg/kg i.p. single dose) was injected on the 10th day of drug treatment. The biochemical estimations revealed that treatment with both these drugs significantly (p < 0.001) increased the serum LDH, cardiac TBARS and catalase levels, while the antioxidant enzyme levels of glutathione and superoxide dismutase were reduced. The administration of rosiglitazone significantly (p < 0.001) reduced the level of serum high density lipoprotein (HDL) and raised the level of low density lipoprotein (LDL) while pioglitazone treatment had shown entirely opposite trend; significantly (p < 0.001) increased HDL level and lowered the LDL level. The transmission electron microscopy and histopathology of rat's cardiac tissue, however, revealed that treatment with both these drugs caused extensive damage to the myocardium as evidenced by condensed chromatin marginates, loss of myofibrils and vacuolization and aggravated doxorubicin-induced cardiomyopathy.