Ameliorative effect of sitagliptin and its cardinal mechanisms in methionine induced- hepatotoxicity in rats

Abstract

Background/ aim: High methionine (Met) (a precursor for homocysteine) diet is a risk factor for non-alcoholic fatty liver disease (NAFLD). This work demonstrated the hepatic effects of feeding western diet enriched with Methionine. Additionally, we evaluated the anti-oxidative properties of sitagliptin (STG) (an antidiabetic drug) which, counteract the negative effects of high Met diet. Methodology: Forty adult male Wister albino rats, divided into 4 group (10 rats/group) normal diet (control and STG groups), or high Methionine enriched diet, 1.5 % Methionine (Met and Met + STG treated groups) for 35 days. Rats were either treated with vehicle (control, Met groups) or Sitagliptin, 100 mg/kg/day (STG, Met + STG groups). Investigations were Lipid profile, liver functions test, serum homocysteine, iron, ferritin, liver reduced glutathione (GSH), serum MDA level and histopathological investigations. Results: Met resulted in significant increase in LDL and cholesterol with significant decrease in HDL. Moreover, it had resulted in significant increase ALT and AST, with significant increase serum iron and homocysteine with no effect on serum ferritin, and significant decrease in tissue reduced glutathione as an antioxidant enzyme. STG with normal control diet had positive effects on different parameters. Treatment with STG has resulted in an improvement in most of altered parameters. Conclusions: Our findings suggest that Met induced NAFLD could be related to increase serum iron, homocysteine levels as an inflammatory activator factors and antioxidant machinery defects and the ameliorating role of STG in this type of induced hepatotoxicity. Keywords