Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats

被引:95
作者
de David, Cintia [1 ]
Rodrigues, Graziella [1 ]
Bona, Silvia [1 ]
Meurer, Luise [1 ]
Gonzalez-Gallego, Javier [2 ,3 ]
Jesus Tunon, Maria [2 ,3 ]
Marroni, Norma Possa [1 ]
机构
[1] Univ Fed Rio Grande do Sul, Porto Alegre Clin Hosp, Lab Expt Hepatol & Physiol, BR-90046900 Porto Alegre, RS, Brazil
[2] Univ Leon, Inst Biomed, E-24071 Leon, Spain
[3] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Leon 24071, Spain
关键词
quercetin; thioacetamide; hepatotoxicity; oxidative stress; KAPPA-B ACTIVATION; NITRIC-OXIDE SYNTHASE; FULMINANT HEPATIC-FAILURE; SIGNAL-REGULATED KINASE; OXIDATIVE STRESS; PROTEIN-KINASE; CELL-DEATH; GLUTATHIONE-PEROXIDASE; SUPEROXIDE-DISMUTASE; REPERFUSION INJURY;
D O I
10.1177/0192623311418680
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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-ERK1/2 (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.
引用
收藏
页码:949 / 957
页数:9
相关论文
共 75 条
[71]   Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat [J].
Wu, Hsing-Hui ;
Hsiao, Tzu-Yu ;
Chien, Chiang-Ting ;
Lai, Ming-Kuen .
JOURNAL OF BIOMEDICAL SCIENCE, 2009, 16
[72]   OPPOSING EFFECTS OF ERK AND JNK-P38 MAP KINASES ON APOPTOSIS [J].
XIA, ZG ;
DICKENS, M ;
RAINGEAUD, J ;
DAVIS, RJ ;
GREENBERG, ME .
SCIENCE, 1995, 270 (5240) :1326-1331
[73]   Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways [J].
Yao, Ping ;
Nussler, Andreas ;
Liu, Liegang ;
Hao, Liping ;
Song, Fangfang ;
Schirineier, Anja ;
Nussler, Natascha .
JOURNAL OF HEPATOLOGY, 2007, 47 (02) :253-261
[74]   Protective effect of bicyclol on liver injury induced by hepatic warm ischemia/reperfusion in rats [J].
Yao, Xiao-min ;
Chen, Hui ;
Li, Yan .
HEPATOLOGY RESEARCH, 2009, 39 (08) :833-842
[75]   DRUG-INDUCED LIVER-DISEASE [J].
ZIMMERMAN, HJ .
DRUGS, 1978, 16 (01) :25-45