Background and aim: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol administration. It has been clinically demonstrated possibility of its progression to advanced fibrosis and even cirrhosis. Among the factors initiating this pathology are obesity, insulin resistance, hyperlipidemia. Therefore, we used for experimental NASH therapy hypolipidemic, insulin sensitizing and membrane stabilizing agents (bezafibrate, metformin, betaine and tauroursodeoxycholic acid (TUDCA).Methods: Adult male Wistar rats (n=10/group) were treated for 10 wks with high-fat methionine-choline deficient diet (MCDD) only, or MCDD diet with either metformin (50 mg/kg b.w.), bezafibrate (100 mg/kg), betaine (100 mg/kg) or TUDCA (80 mg/kg) during last 4 wks. 10 rats served as healthy controls. The severity of liver damage was evaluated histologically. Serum and liver lipids and lipoproteins content, serum insulin, glucose, bilirubin, TNF-a , leptin and adiponectin levels and serum marker enzymes activities were measured. Results:. MCDD-fed group had enhanced liver relative mass and severe hepatic steatohepatitis of score stage 3: almost 75% of the parenchyma developed steatosis. Hepatocyte ballooning and inflammatory scoring stage 1were observed. Serum marker enzymes, AlAT, AsAT, alkaline phosphatase, were dramatically activated as compared to healthy control rats. Concentration of hepatic triglycerides, cholesterol and phospholipids were increased, while the serum lipids content was decreased. We noted significant rise of the serum proinflammatory cytokine TNF-a , increase in the serum leptin concentration and blood glucose content, whereas serum insulin and adiponectin levels were decreased. The administration of all studied agents caused significant beneficial changes in most of the histological and biochemical parameters measured. All compounds normalized serum marker enzyme activities.The treatment with either TUDCA or metformine was decreased blood glucose concentration and normalized serum insulin level. A normalization of the serum lipid and lipoprotein parameters was mostly seen in the TUDCA-, betaine- and metformine-treated groups. all compounds significantly decreased liver lipids (triglycerides, cholesterol, phospholipids) content. All the compounds normalized serum adiponectin level, whereas concentration of TNF-a and leptine were decrease only in TUDCA- and betaine-treated groups.Conclusions: 1. The treatment with TUDCA, betaine and metformine and, in the less extent, bezafibrate had a significant hepatoprotectiveb effect in rats with experimental NASH. 2. The clinical implication of this finding is promising for the treatment NASH in the clinics.

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