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Activation of TGF‐β/Smad signaling pathway by high cholesterol diet: possible inhibition by rutin compound
Author(s) -
Alrejaie Salim S.,
AlSharari Shakir,
Hafez M.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1199.5
Subject(s) - rutin , smad , endocrinology , reactive oxygen species , medicine , signal transduction , oxidative stress , transforming growth factor , pharmacology , chemistry , cholesterol , antioxidant , biology , biochemistry
Background High‐cholesterol diet (HCD) increases the oxidative stress in liver resulting in generation of reactive oxygen species (ROS). ROS may activate transforming growth factor beta (TGF‐β) and Mothers Against decapentaplegic Homolog (Smad)signaling pathway leading to hepatotoxicity. Rutin is a natural flavonoid (vitamin p), which possesses an antioxidant activity with protective potential. The aim of the present study was to investigate the potential alleviating effects of rutin against hyper‐cholesterolemia‐induced TGF‐β/Smad signaling pathway activation and hepatotoxicity in rat. Methods Male Wistar rats were divided into four groups: G‐I control (Rat chow), G‐II Rutin (0.2% in rat chow), G‐III HCD (1% cholesterol and 0.5% cholic acid in rat chow) and G‐IV rutin (0.2%) + HCD. Animals received freshly prepared experimental diets for 6 consecutive weeks. In hepatic tissue, gene expressions of TGF‐β, Smad‐2 and Smad‐4 were measured using real time PCR. Results In HCD group, the gene expression levels of TGF‐β, Smad2 and Smad4 significantly increased by8‐, 8.5‐ and 5.3‐folds expressions, compared to the control group. On the other hand, administration of rutin in combination with HCD induced a significant repair of the HCD‐induced alteration in the gene expression of TGF‐β, Smad2 and Smad4 compared to the HCD group expression levels. Conclusion Our findings revealed that TGF‐β/Smad signaling pathway is involved in the hepatotoxicity induced by HCD and rutin inhibits hepatotoxicity via suppressing this pathway. Therefore, rutin might be considered as a protective agent for hepatotoxicity. Support or Funding Information The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research project no NFG‐14‐02‐13