Combination of biotransformation and metabolomics reveals tolfenpyrad-induced hepatocytotoxicity

• 全文链接

生物转化和代谢组学的结合揭示了唑虫酰胺诱导的肝细胞毒性

关键词：

来源：

Science of The Total Environment 期刊

全文链接：

//agri.nais.net.cn/topic/downloadFile/1d20d4be-490f-4206-8379-00655c7e73df

来源地址：

https://www.sciencedirect.com/science/article/pii/S0048969724054706?via%3Dihub

资源所属：

茶学研究专题

类型：

学术文献

语种：

英语

原文发布日期：

2024-11-15

摘要：

Tolfenpyrad (TFP) is an extensively used pesticide that inevitably leads to human exposure to both TFP and its transformation product residues. However, the biotransformation of TFP in humans has not been elucidated, and the toxicity of TFP along with its biotransformation products remains largely unknown. In this study, the biotransformation process of TFP was investigated using human liver microsomes and human hepatic cells. Endogenous metabolic changes in the cells were studied to investigate the hepatocytotoxicity of TFP at environmentally relevant concentrations. Fourteen phase I biotransformation products and four phase II TFP products were characterized, among which twelve products were identified for the first time. The oxidative product tolfenpyrad-benzoic acid (PT-CA) was particularly abundant and stable. Further hepatotoxicity assessments and metabolic studies demonstrated comparable metabolic profiles for TFP and PT-CA in HepG2 cells, with both significantly disrupting purine and glutathione metabolism. These processes are closely associated with oxidative stress, mitochondrial damage, and cell death. Our results provide novel perspectives on the biotransformation, metabolism, and hepatotoxicity of TFP, thereby highlighting the non-negligible toxicity of its crucial biotransformation product PT-CA in environmental risk assessments.