title: Role of quercetin in preventing thioacetamide-induced liver injury in rats.
abstract: In hepatic toxicity induced in rats by two injections of thioacetamide (TAA, 350 mg/kg with an interval of 8 hr), the action of quercetin was investigated. After 96 hr, TAA administration resulted in hepatic necrosis, significant increases in serum transaminase activity, and increases in hepatic lipoperoxidation. Thioacetamide-induced hepatotoxicity also showed changes in antioxidant enzymes in the liver of rats, with alterations in p-ERK 1/2 (phosphorylated extracellular-signal related kinase 1/2) as well as an imbalance between proapototic protein Bax and anti-apoptotic protein Bcl-2 expression. With administration of the flavonoid quercetin (50 mg/Kg i.p.) for four consecutive days following TAA, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were close to normal values in rats. Histological findings suggested that quercetin had a preventive effect on TAA-induced hepatic necrosis. Quercetin treatment caused significant decreases in lipid peroxide levels in the TAA-treated rats, with some changes in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Quercetin also inhibited the change of the p-ERK1/2 by TAA and significantly prevented the increase in Bax/Bcl-2 ratio, thus preventing apoptosis. Findings indicate that quercetin may have a preventive effect on TAA-induced hepatotoxicity by modulating the oxidative stress parameters and apoptosis pathway.
authors: Laboratory of Experimental Hepatology and Physiology, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors: Cíntia
authors: C
authors: de David
authors: Graziella
authors: G
authors: Rodrigues
authors: Silvia
authors: S
authors: Bona
authors: Luise
authors: L
authors: Meurer
authors: Javier
authors: J
authors: González-Gallego
authors: María Jesús
authors: MJ
authors: Tuñón
authors: Norma Possa
authors: NP
authors: Marroni
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000032:analysis; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D018384:Oxidative Stress; D010766:Phosphorylation; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013853:Thioacetamide / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C494828:Bax protein, rat; D008054:Lipid Peroxides; D051028:bcl-2-Associated X Protein; D013853:Thioacetamide; D011794:Quercetin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase