Atorvastatin attenuates inflammation and oxidative stress induced by ischemia/reperfusion in rat heart via the Nrf2 transcription factor.

Abstract

The role of atorvastatin in inflammation and oxidative stress induced by ischemia/reperfusion is currently not well understood. The aim of this study was toinvestigate whether atorvastatin modulates neutrophil accumulation, TNF-α induction and oxidative stress and to examine the possible role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in an ischemia/reperfusion injured rat heart model. Rats were randomly assigned into tosham operation group, myocardial ischemia/reperfusion (MI/R) group, MI/R + atorvastatin group. Myocardial infarct area, myeloperoxidase (MPO), serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels were monitored. The results indicate that compared to MI/R, atorvastatin reduced myocardial infarction area, MPO level, serum CK and LDH levels, and both serum and myocardial TNF-αproduction. In addition, atorvastatin increased SOD and GSH-PX activity and decreased MDA content. Atorvastatin also enhanced levels of Nrf2 and heme oxygenase-1. In summary, our data suggests that atorvastatin exerts significant cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.