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Rutin attenuates high cholesterol diet‐induced hepatotoxicity in rat model via regulation of tumor suppressor genes; p53 and caspase‐3 and P21
Author(s) -
Alhoshani Ali,
Hafez Mohammed 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.1267.4
Subject(s) - oxidative stress , rutin , endocrinology , medicine , apoptosis , fatty liver , pathogenesis , cholesterol , caspase 3 , steatosis , chemistry , pharmacology , antioxidant , disease , biochemistry , programmed cell death
Hypercholesterolemia‐induced oxidative stress has been implicated in the pathogenesis of various disease including cardiovascular disorders and non‐alcoholic fatty liver disease (NAFLD). Tumor suppressor genes such as p53 play a central role in NAFLD. p53 activation facilitates apoptosis, oxidative stress, steatosis and injury. Levels of p21 often determine the cellular response to different stress induced by drug and others. Caspase‐3‐mediated cleavage of p21. This study was designed to investigate the potential protective effects of dietary antioxidant rutin (RT) combination with high cholesterol diet (HCD) induced hepatotoxicity in male Wistar albino rats. Twenty four male Wistar rats were used in the present study. Animals were divided into four groups; (1) control, (2) RT, (3) HCD and (4) HCD+RT. Animals received freshly prepared experimental diets for 6 consecutive weeks. In plasma, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were estimated. In hepatic tissue, gene expressions of p53 and caspase‐3 and P21 were measured using real time PCR. Rats fed with HCD for 6 weeks had significant increase in plasma ALT and AST levels compared to control and HCD+RT groups. In the current study, HCD increase p53 and caspase‐3 mRNA expression and reduced the mRNA expression P21. Rutin in combination with HCD induced a significant protective effect against the alteration in p53 and caspase‐3 and P21 genes expression. In conclusion, our findings demonstrated that rutin could attenuate the hepatotoxicity induced by HCD in rat model via regulation of tumor suppressor genes.