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 five groups (10 each): (i) control; (ii) mice were injected intraperitoneally with 50 mu L carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 mu L/g three times per week for four weeks; (iii) linagliptin was administered orally in a daily dose of 10 mg/kg simultaneously with CCl4; (iv) silymarin was administered orally in a daily dose of 200 mg/kg concomitantly with CCl4; and (v) only linagliptin was administered. Hepatic injury was manifested in the CCl4 group by elevation of biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), and hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of alpha-smooth muscle actin (alpha-SMA), as well as increased liver tissue oxidative stress parameters, transforming growth factor-beta 1 (TGF-beta 1), and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis, evident histopathologically with reduced METAVIR score and alpha-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-beta 1, and mTOR, which 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.

Automated summary

Linagliptin may prevent the progression of liver fibrosis by suppressing oxidative stress, TGF-beta 1, and mTOR, leading to improved liver injury and fibrosis.