de David Cíntia, Rodrigues Graziella, Bona Silvia, Meurer Luise, González-Gallego Javier, Tuñón María Jesús, Marroni Norma Possa
Laboratory of Experimental Hepatology and Physiology, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Toxicol Pathol. 2011 Oct;39(6):949-57. doi: 10.1177/0192623311418680. Epub 2011 Sep 1.
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.
在通过两次注射硫代乙酰胺(TAA,350mg/kg,间隔8小时)诱导大鼠产生肝毒性的实验中,研究了槲皮素的作用。96小时后,给予TAA导致肝坏死、血清转氨酶活性显著升高以及肝脏脂质过氧化增加。硫代乙酰胺诱导的肝毒性还表现为大鼠肝脏抗氧化酶的变化,p-ERK 1/2(磷酸化细胞外信号调节激酶1/2)发生改变,同时促凋亡蛋白Bax和抗凋亡蛋白Bcl-2的表达失衡。在TAA给药后连续四天腹腔注射类黄酮槲皮素(50mg/Kg),大鼠血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性接近正常水平。组织学结果表明,槲皮素对TAA诱导的肝坏死有预防作用。槲皮素处理使TAA处理的大鼠脂质过氧化物水平显著降低,抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)也有一些变化。槲皮素还抑制了TAA引起的p-ERK1/2变化,并显著阻止了Bax/Bcl-2比值的升高,从而防止细胞凋亡。研究结果表明,槲皮素可能通过调节氧化应激参数和细胞凋亡途径对TAA诱导的肝毒性具有预防作用。