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
,
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.