title: Association between paraoxonases gene expression and oxidative stress in hepatotoxicity induced by CCl4.
abstract: Objectives. The purpose of the study is to evaluate the hepatoprotective effect of rutin in carbon tetrachloride- (CCl4-) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl4. Group IV was administered rutin after 48 h of CCl4 treatment. Liver enzymes level, lipid profile, lipid peroxidation, and hydrogen peroxide were measured. The genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl4 group showed significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H2O2), and lipid profile and a significant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-δ), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl4 to control values. Conclusion. CCl4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective effect through enhancing the antioxidant genes.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al-Rejaie
authors.affiliation: Riyadh Regional Laboratory and Blood Bank, Riyadh 11451, Saudi Arabia.
authors.forename: Saad M
authors.initials: SM
authors.lastname: Alsurayea
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D012431:Rutin; D002251:Carbon Tetrachloride; D043303:Aryldialkylphosphatase