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

Abstract

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,P53and 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/Smadsignaling 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.