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 µL carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 µL/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 (α-SMA), as well as increased liver tissue oxidative stress parameters, transforming growth factor-ß1 (TGF-ß1), 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-ß1, 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.

Hepatoprotective effect of trans-Chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis.

The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4 and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-ß1, collagen content), hepatic inflammation (TNF-α), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti-oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent.