Hepatoprotective effect of Linagliptin against liver fibrosis induced by carbon tetrachloride in mice

The current study aimed to investigate linagliptin for its potential role in the prevention of liver fibrosis progression. Balb-C mice were randomly allocated into 5 groups (10 each), (1) control, (2) mice were injected intraperitoneally with 50 μl carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 μl /g 3 times a week for 4 weeks, (3) linagliptin was orally administered in a dose of 10 mg/kg/day simultaneously with CCl4, (4) silymarin was orally in a dose of 200 mg/kg/day concomitantly with CCl4, (5) linagliptin only. Hepatic injury was manifested in CCl4 group by elevation of biochemical parameters; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of α-smooth muscle actin (α-SMA), also, increased liver tissue oxidative stress parameters, transforming growth factor-β1 (TGF-β1) and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis; evident histopathologically with reduced METAVIR score and α-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-β1, and mTOR, this was associated with improvement of serum biochemical parameters; ALT and AST. In conclusion, linagliptin might help to protect the liver against persistent injury-related consequences.