Influence of pioglitazone on experimental heart failure and hyperlipidemia in rats

To investigate the effect of pioglitazone on isoproterenol-induced heart failure and high-fructose diet-induced metabolic changes in rats.

Three doses of pioglitazone (Pio - 3, 10, 30 mg/kg, po) were tested in male Wistar rats. In the Heart Failure (HF) group, treatment was followed by Isoproterenol (ISO) injection. The markers for HF, such as enzyme estimation, relative heart weight, and antioxidant status, were evaluated. In another group, metabolic disturbances were induced by High Fructose Diet (HFD). The influence of Pio treatment on Systolic Blood Pressure (SBP), serum glucose, Triglycerides (TG), Total Cholesterol (TC), and High-Density Lipoprotein (HDL)-cholesterol (HDL-c) were determined.

The results indicated that Pio at 10 mg increased significantly (P<0.05) the Lactate Dehydrogenase (LDH), Creatinine Kinase-MB (CK-MB), and antioxidant enzyme levels as compared to ISO. The high dose of Pio (30 mg) enhanced (P<0.05) Aspartate Transaminase (AST), Alanine Transaminase (ALT), Lipid Peroxidation (LPO),and relative heart weight in addition to increased LDH, CK-MB, and antioxidant enzyme activity. In the HFD group, a dose-dependent inhibitory effect was observed. Pio at 3 mg significantly reduced (P<0.05) elevated glycemia, TG, and SBP as compared to HFD rats. Further, the higher doses of Pio (10 and 30 mg) enhanced the inhibitory effect on glucose, TG, and SBP besides elevating the HDL-c levels. However, none of the tested doses of Pio significantly altered the TC level in HFD rats.

The observations suggest that Pio exhibits anti-diabetic and anti-hypertensive effects and also partially corrected the hyperlipidemia, but the treatment augmented the cardiac damage associated with ISO. The antioxidant property of Pio appears to have a limited role in protecting the ISO-mediated heart damage.