Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Mohali, Punjab-160 062, India.
Phytother Res. 2010 Jan;24(1):119-28. doi: 10.1002/ptr.2883.
Diethylnitrosamine (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.
二乙基亚硝胺（DEN）是一种强有力的肝癌致癌物，存在于烟草烟雾、加工肉类以及各种食品中。槲皮素（QC）是一种天然存在的类黄酮，具有出色的抗氧化特性。本研究旨在探讨 QC 对 DEN 诱导的 Sprague-Dawley（SD）大鼠肝毒性的化学预防作用。连续 5 天给予 DEN（200mg/kg）处理后，给予 QC（10、30 和 100mg/kg）。在最后一次给予 QC/生理盐水处理后 24 小时处死动物。 DEN 导致肝毒性，表现在肝脏中丙二醛（MDA）升高和谷胱甘肽（GSH）水平降低。 DEN 处理组的血浆天冬氨酸转氨酶（AST）和血浆丙氨酸转氨酶（ALT）水平显著升高。使用单细胞凝胶电泳（SCGE）测定评估 DEN 诱导的 DNA 损伤。 DEN 处理组的 TUNEL 阳性细胞数量显著增加。QC 在所有测试剂量下均能恢复 AST、ALT 和 GSH 水平。在 10 和 30mg/kg 的 QC 剂量下，MDA 水平和细胞形态得到恢复。此外，QC 改善了 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，可作为一种良好的化学预防剂。
