Cytotoxicity of mequindox and its metabolites in HepG2 cells in vitro and murine hepatocytes in vivo

文献类型： 外文期刊

第一作者： Liu, Yingchun

作者： Liu, Yingchun;Jiang, Wei;Chen, Yongjun;Zeng, Peng;Xue, Feiqun;Wang, Quan;Liu, Yanyan

作者机构：

关键词： Mequindox;Metabolite;Cytotoxicity;HepG2 cell;Hepatocyte

期刊名称：MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS （ 影响因子：2.873； 五年影响因子：2.69 ）

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收录情况： SCI

摘要： Mequindox, a quinoxaline 1,4-dioxide, is widely used as a feed additive in the Chinese livestock industry because of its effective antibacterial properties. Many recent studies have found that mequindox is rapidly metabolized to numerous metabolites following administration to animals. There have, however, been few reports describing the cytotoxicity of mequindox metabolites. In this study, HepG2 cells were treated with mequindox (0, 2, 10,50 or 100 mu g/ml) or its major metabolites (0,40, 100,250 or 500 mu g/ml) for 24 h. Mice were administrated with mequindox (0, 50,200 or 500 mg/kg.bw) for five days. DNA damage in the HepG2 cells and mouse hepatocytes was then assessed using an SCGE assay. The cell cycle of the HepG2 cells was also determined by flow cytometry. Mequindox was found to induce cell cycle arrest to the G2/M phase and cause dose-dependent DNA damage in HepG2 cells in vitro and in murine hepatocytes in vivo. Compared with mequindox, the major metabolites had much smaller effects on the cell cycle and caused much less DNA damage in HepG2 cells. And the results indicated that the process of metabolites formed by reduction of the MEQ acetyl group or reduction of the N -> O groups could contribute to DNA damage in murine hepatocytes in vivo. (C) 2016 Elsevier B.V. All rights reserved.

分类号： R394

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