Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats
Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats
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DOI：
10.1177/0192623311418680
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发表时间：
2011-10-01
影响因子：
1.5
通讯作者：
Marroni, Norma Possa
中科院分区：
文献类型：
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作者：
de David, Cintia;Rodrigues, Graziella;Marroni, Norma Possa
在两次注射硫代乙酰胺（TAA，350 mg/kg，间隔 8 小时）引起的大鼠肝毒性中，研究了槲皮素的作用。 96小时后，给予TAA导致肝坏死、血清转氨酶活性显着增加以及肝脂质过氧化增加。硫代乙酰胺诱导的肝毒性还显示大鼠肝脏中抗氧化酶的变化，包括 p-ERK1/2（磷酸化细胞外信号相关激酶 1/2）的变化以及促凋亡蛋白 Bax 和抗凋亡蛋白 Bcl-2 表达之间的不平衡。 TAA 后连续四天给予类黄酮槲皮素 (50 mg/Kg i.p.)，大鼠血清天冬氨酸转氨酶 (AST) 和丙氨酸转氨酶 (ALT) 活性接近正常值。组织学结果表明槲皮素对TAA引起的肝坏死具有预防作用。槲皮素治疗导致 TAA 治疗大鼠的脂质过氧化物水平显着降低，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) 发生一些变化。槲皮素还能抑制TAA对p-ERK1/2的改变，并显着阻止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。
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.