Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4 induced liver toxicity in Wistar rats

Environ Toxicol. 2018 Mar;33(3):361-369. doi: 10.1002/tox.22523. Epub 2017 Dec 18.

Abstract

This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-β, and α-SMA were also assessed; CCl4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties.

Keywords: CCL4; D-Limonene; antifibrotic; fibrosis and liver.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Carbon Tetrachloride
  • Cyclohexenes / therapeutic use*
  • Glutathione / metabolism
  • Limonene
  • Liver / drug effects
  • Liver / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Terpenes / therapeutic use*
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cyclohexenes
  • NF-kappa B
  • Terpenes
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Limonene
  • Carbon Tetrachloride
  • Glutathione