Hepatoprotective effect of dipeptidyl peptidase-4 inhibitor sitagliptin against carbon tetrachloride-induced liver fibrosis in mice

Abstract

Background and Aim Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor that is used worldwide to ameliorate hyperglycemia and insulin insensitivity-induced dysmetabolism. The current study assessed the effect of sitagliptin as well as silymarin (the standard hepatoprotective drug) against experimentally carbon tetrachloride (CCl4)-induced liver toxicity in male mice. Materials and methods Mice chronic liver fibrosis models were established and divided into olive oil-induced control group, CCl4-induced model group, silymarin-treated group, and sitagliptin-treated group. Hepatic fibrotic changes were evaluated by measuring hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), histopathological score, activation of hepatic stellate cells (α-smooth muscle actin expression with special stain), and oxidative stress (malondialdehyde, glutathione, total nitrate/nitrite, and manganese superoxide dismutase levels). Results The injection of mice with CCl4 for 7 weeks resulted in a marked elevation of hepatic fibrotic changes and reduction of glutathione level; both silymarin and sitagliptin therapy showed a significant decrease in the fibrotic changes and a significant increase in endogenous antioxidants. Conclusion This study shows that sitagliptin ameliorates hepatic fibrosis in mice and announces a new strategy for treating hepatic fibrosis in humans.

Keywords

• carbon tetrachloride
• liver fibrosis
• silymarin
• sitagliptin