Gene Expression Analysis for Statin-induced Cytotoxicity from Rat Primary Hepatocytes

Abstract Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins al-so have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies re-currently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients sug-gesting possible liver toxicity due to statins. This ob-servation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism respon-sible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their bio-logical functions. It is of interest that those genes have function related to response to stress in particular im-munity and defense in cells. Our study provided the ba-sic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes. Keywords: cytotoxicity, gene expression, hepatocyte, microarray, statin