ANTI-ATHEROSCLEROTIC POTENTIAL OF PIOGLITAZONE AND N-ACETYLCYSTEINE

Atherosclerosis involves disturbances in endothelium and the resultant cascade of inflammatory reactions involving generation of ROS (Reactive Oxygen Species). Peroxisome proliferator-activated receptor-g (PPAR-g) receptors are more expressed during atherosclerosis process and its stimulation results in inhibition of formation of atherosclerotic plaque. N-acetylcysteine (NAC) stimulates GSH (glutathione) formation and thus helps in scavenging ROS.  Thus, the purpose of present study is to explore the role of PPAR-g agonist (pioglitazone) and N-acetylcysteine in atherosclerosis.  Endothelial injury in hyper-lipidemic rat was produced in the femoral artery. The effect of chronic treatment of pioglitazone, N-acetylcysteine and their combination was evaluated by measuring serum HDL, LDL, triglyceride, total cholesterol and lesion index.  Pioglitazone and N-acetylcysteine treated rats showed higher levels of HDL and lower levels of LDL, triglycerides and total cholesterol as compared to model control animals (diet + endothelial injury model).  Combination of both pioglitazone and N-acetylcysteine produced synergistic action with respect to lipid level.  N-acetylcysteine treated animals showed high GSH levels in the liver. Femoral artery lesion index was significantly less in the groups treated with pioglitazone (1.3±0.09), N-acetylcysteine (3.17±0.28) as well as their combination (1.02±0.07) when compared with model control group (4.57±0.19).  From all above results, it can be concluded that PPAR-g agonist (pioglitazone) and N-acetylcysteine are having anti-proliferative, anti-oxidant and/or anti-inflammatory activity which may be responsible for anti-atherosclerotic activity.