The hepatoprotective effect of fraxetin on carbon tetrachloride induced hepatic fibrosis by antioxidative activities in rats

Int Immunopharmacol. 2013 Nov;17(3):543-7. doi: 10.1016/j.intimp.2013.08.006. Epub 2013 Aug 27.

Abstract

The aim of the study was to investigate the potentially protective effects of fraxetin on carbon tetrachloride (CCl4) induced oxidative stress and hepatic fibrosis in Sprague-Dawley rats. In this study, rats were divided into five groups, including normal controls, model, silymarin as the positive control, fraxetin 20 mg/kg and fraxetin 50 mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked. The levels of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and antioxidant enzymes such as catalase, SOD and glutathione peroxidase (GSH-Px) were determined after fraxetin administration. The hydroxyproline levels and histopathologic examinations of hepatocyte fibrosis were also determined. We found that fraxetin at doses of 20 and 50 mg/kg for 8 weeks significantly reduced the levels of TBARS and protein carbonyls compared with CCl4 group. Fraxetin significantly increased the activities of catalase, SOD and GSH-Px in the liver. We also found that fraxetin prevented CCl4 induced hepatic fibrosis by histological observations. These results indicate that fraxetin exhibits potent protective effects against CCl4 induced oxidative stress and hepatic fibrosis.

Keywords: Antifibrotic; Antioxidant; Carbon tetrachloride (CCl(4)); Fraxetin; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Coumarins / pharmacology
  • Coumarins / therapeutic use*
  • Glutathione Peroxidase / metabolism
  • Hydroxyproline / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Male
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Coumarins
  • Protective Agents
  • fraxetin
  • Carbon Tetrachloride
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Hydroxyproline