Antioxidant and Antimutagenic Effect of Quercetin against DEN Induced Hepatotoxicity in Rat
Antioxidant and Antimutagenic Effect of Quercetin against DEN Induced Hepatotoxicity in Rat
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DOI：
10.1002/ptr.2883
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发表时间：
2010-01-01
影响因子：
7.2
通讯作者：
Jena, G. B.
中科院分区：
文献类型：
--
作者：
Gupta, C.;Vikram, A.;Jena, G. B.
二乙基亚硝胺（DEN）是一种强效的肝癌致癌物，存在于烟草烟雾、加工肉类以及不同的食品中。槲皮素（QC）是一种天然存在的类黄酮，具有优异的抗氧化性能。本研究旨在探讨QC对DEN诱导的SD大鼠肝毒性的化学保护作用。在DEN （200 mg/kg）处理后，连续5天给予槲皮素（10、30和100 mg/kg）。最后一剂QC/生理盐水处理后24 h处死动物。肝内丙二醛（MDA）升高和谷胱甘肽（GSH）水平降低，可见DEN诱导的肝毒性。DEN治疗组血浆天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平显著升高。采用单细胞凝胶电泳（SCGE）法评估DEN诱导的DNA损伤。DEN处理组TUNEL阳性细胞数量明显增加。槲皮素在所有测试剂量下都能恢复AST、ALT和GSH水平。在剂量为10和30 mg/kg的QC下，观察到MDA水平和细胞形态的恢复。此外，QC可改善DEN诱导的DNA损伤和细胞凋亡。结果表明，QC可改善DEN诱导的大鼠肝毒性，可能是一种良好的化学保护剂。版权所有John Wiley & Sons， Ltd. 2009
Diethyinitrosamine (DEN), a potent hepatocarcinogen, is found in tobacco smoke, processed meat as well as in different food products. Quercetin (QC), a naturally occurring flavonoid has excellent antioxidant properties. The present study was aimed to investigate the chemoprotective potential of QC against DEN induced hepatotoxicity in Sprague-Dawley (SD) rats. Quercetin was administered (10, 30 and 100 mg/kg) for 5 consecutive days after DEN (200 mg/kg) treatment. The animals were killed 24 h after the last dose of QC/saline treatment. The DEN induced hepatotoxicity was evident by elevated malondialdehyde (MDA) and decreased glutathione (GSH) levels in the liver. A significant increase in the levels of plasma aspartate transaminase (AST) and plasma alanine transaminase (ALT) was observed in the DEN treated group. The DEN induced DNA damage was evaluated using a single cell gel electrophoresis (SCGE) assay. A significant increase in the number of TUNEL positive cells was observed in the DEN treated group. Quercetin restored AST, ALT and GSH levels at all the tested doses. Restoration of the MDA level and cellular morphology was observed at doses of 10 and 30 mg/kg of QC. Further, DEN induced DNA damage and apoptosis was ameliorated by QC. The results indicate that QC ameliorates the DEN induced hepatotoxicity in rats and can be a candidate for a good chemoprotectant. Copyright (C) 2009 John Wiley & Sons, Ltd.