Monitoring tryptophan metabolism after exposure to hexaconazole and the enantioselective metabolism of hexaconazole in rat hepatocytes in vitro
文献类型: 外文期刊
第一作者: Wang, Yao
作者: Wang, Yao;Zhu, Wentao;Wang, Xinru;Zhang, Ping;Yan, Jin;Zhou, Zhiqiang;Qiu, Jing
作者机构:
关键词: Hexaconazole;Enantioselevtive metabolism;Cytotoxicity;Tryptophan metabolism
期刊名称:JOURNAL OF HAZARDOUS MATERIALS ( 影响因子:10.588; 五年影响因子:10.129 )
ISSN:
年卷期:
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收录情况: SCI
摘要: In the present study, the enantioselective metabolism, cytotoxicity of hexaconazole and its influence on tryptophan metabolism in rat hepatocytes in vitro were investigated. Following the exposure of primary rat hepatocytes to rac-hexaconazole, the concentrations of its enantiomers in the media were determined by chiral high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The half-lives (t(1/2)) of (+)-hexaconazole and (-)-hexaconazole were 5.17 hand 19.80 h, respectively, indicating that the metabolic process was enantioselective with (-)-hexaconazole enrichment. Using the MTT method, the EC50 values of rac-hexaconazole, (+)-hexaconazole and (-)-hexaconazole after 12 h of exposure were determined to be 71.62, 62.71 and 67.94 mu M, respectively. Tryptophan metabolism was monitored using metabolomics profiling techniques. Hexaconazole and its enantiomers caused the down-regulation of tryptophan levels and the up-regulation of kynurenine (KYN) levels, suggesting a role for hexaconazole in the activation of the KYN pathway and providing information for the mechanism of its toxicity. (C) 2015 Elsevier B.V. All rights reserved.
分类号: TB1
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