Rutin Attenuates Hepatotoxicity in High-Cholesterol-Diet-Fed Rats

Oxid Med Cell Longev. 2016;2016:5436745. doi: 10.1155/2016/5436745. Epub 2016 Apr 27.


Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity. Quantitative real time-PCR was carried out to evaluate the expression levels of genes in TGF-β/Smad signaling pathway. Results. Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (TGF-β), Mothers Against Decapentaplegic Homolog 2 (Smad-2), Mothers Against Decapentaplegic Homolog 4 (Smad-4), Bcl-2-binding component 3 (Bbc3), caspase-3, P53 and Interleukin-6 (IL-6) and decrease in the expression levels of Cyclin depended kinase inhibitor (P21) and Interleukin-3 (IL-3) in hepatic cells. Conclusion. TGF-β/Smad signaling pathway is involved in HCD-induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Body Weight / drug effects
  • Caspase 3 / metabolism
  • Cholesterol / adverse effects*
  • Diet, High-Fat / adverse effects*
  • Interleukins / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / blood
  • Liver Diseases / drug therapy*
  • Liver Diseases / enzymology
  • Male
  • Organ Size / drug effects
  • Rats, Wistar
  • Rutin / pharmacology
  • Rutin / therapeutic use*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism


  • Interleukins
  • Smad Proteins
  • Transforming Growth Factor beta
  • Rutin
  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 3