Ahmed M Kabel^{1, 2,}, Hany M Borg³

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that may progress to advanced fibrosis and cirrhosis. Yet, its pathogenesis is not fully understood. The aim of this work was to study the possible protective effect of atorvastatin and pioglitazone on non-alcoholic steatohepatitis induced by high fat diet (HFD) in rats. Sixty male albino rats were divided into two main groups, the normal control group (ten rats) and HFD group (fifty rats) which was further subdivided into five subgroups (ten rats each) one of them received HFD+normal saline (NASH group), the 2nd received HFD + vehicle (gum tragacanth), the 3rd received HFD+atorvastatin, the 4th received HFD+ pioglitazone and the last group received HFD+atorvastatin and pioglitazone. At the end of the study, animals were killed and blood samples were collected for estimations of serum ALT, AST, ALP, TNF-α, triglycerides, total cholesterol, glucose, insulin and HOMA-IR. Also, samples of liver were taken and studied for hepatic triglycerides, malondialdehyde, free fatty acids and histopathological analysis. Atorvastatin lowered efficiently serum ALT, AST, ALP, TNF-α, total cholesterol, triglycerides, hepatic triglycerides, malondialdehyde and free fatty acids, together with marked improvement in histopathology of liver steatohepatitis, but, produced insignificant effects on fasting blood glucose, serum insulin and HOMA-IR. On the other hand, administration of pioglitazone, whether alone or in combination with atorvastatin induced significant improvement of all the above mentioned parameters. In conclusion, if the prominent feature in NASH is insulin resistance, we recommend the use of pioglitazone, while atorvastatin will be needed if the prominent features is hyperlipidemia and both drugs simultaneously if there are both hyperlipidemia and insulin resistance.

statins, thiazolidinediones, non-alcoholic steatohepatitis, rats