Monitoring tryptophan metabolism after exposure to hexaconazole and the enantioselective metabolism of hexaconazole in rat hepatocytes in vitro

作者：Wang Yao; Zhu Wentao; Qiu Jing; Wang Xinru; Zhang Ping; Yan Jin; Zhou Zhiqiang^*

来源：Journal of Hazardous Materials, 2015, 295: 9-16.

DOI：10.1016/j.jhazmat.2015.04.006

• Hexaconazole
• Enantioselevtive metabolism
• Cytotoxicity
• Tryptophan metabolism

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.

• 出版日期2015-9-15
• 单位中国农业大学; 中国农业科学院农业质量标准与检测技术研究所