Curcumin-mediated effects on anti-diabetic drug-induced cardiotoxicity.

The present study was designed to compare the cardiotoxicity of two very commonly used anti-diabetic drugs namely pioglitazone (Pio) and metformin (Met); and to study the effects of curcumin (Curc) against these drug-induced cardiotoxicity. Curc, being an anti-oxidant molecule and having cardio-protective potential, can have promising synergistic effects in reducing the cardiac stress induced by anti-diabetic therapies. Various dose and time-dependent cell viability and oxidative stress assays were conducted to study cardiotoxic side-effects and Curc-mediated effects in cardiomyoblasts. Effects of Curc were also studied in hyperglycaemia induced cardiac stress in the presence of drugs. Quantitative assays for cell growth, reactive oxygen species (ROS) generation, lipid peroxidation and mitochondrial permeability followed by anti-oxidant enzymes and caspases activity assays were done to study the mechanism of action of the induced cardiotoxicity. Significant dose and time mediated deleterious effects of Pio and Met were witnessed. Oxidative stress studies showed a remarkable increase in ROS with increasing dose of anti-diabetic drugs. Increased caspase activity and altered mitochondrial integrity were also witnessed in presence of Met and Pio in cardiomyoblasts. These alterations were found to be significantly reduced when treated with Curc simultaneously. The study confirms that Met and Pio exert toxic effects on cardiac cells by generating oxidative stress. Curc, being an anti-oxidative molecule, can suppress this effect and, therefore, can be used as a supplement with anti-diabetic drugs to suppress the induced cardiac stress.