Cardioprotective Effects of Atorvastatin Are Mediated Through PPARγ in Paraquat-Exposed Rats

Background: Paraquat poisoning is one of leading intoxication worldwide without an effective antidote and treatment protocol. Among the other organs, cardiotoxicity of paraquat has been frequently reported. Aim: The protective effects of atorvastatin (STN) on paraquatinduced cardiotoxicity and the role of peroxisome proliferator-activated receptors gamma in the mediation of STN effects were investigated. Methods: Forty-two male Wistar rats were aliquoted into control or test groups. The animals in test groups in addition of paraquat received saline normal (PQ), pioglitazone (PGT), atorvastatin (STN), PGT + STN, PGT + GW9662, and/or STN + GW9662 for 14 days. Results: PGT and STN lowered lipid peroxidation rate, nitric oxide concentration, and activity of myeloperoxidase and CK/MB in the heart. PGT and STN protected from thiol molecules reduction and PQ-induced histopathological injuries. STN regulated the PQ-induced upregulation of COX-II expression in the heart. All STN-related protective effects were reversed by GW9662 as PPAR gamma antagonist. Conclusions: These data suggest a cardioprotective effect for STN against the PQ-induced inflammation and oxidative stress. The pharmacologic approach of these findings indicates that STN through PPAR gamma pathway lowered the PQ-induced cardiotoxicity.