Wei Shuilin, Wu Mengjing, Qin Quanzhi, Chen Chunxia, Huang Huan, Wen Zhongqing, Huang Junli, Xie Xixiang, Su Rixiang, Zhou Xing, Qin Jian, Liu Xiaoxia, Chen Xiaoyu
Department of Pharmacy, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China.
Department of Pharmacy, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China.
Toxicol Lett. 2025 May 1;407:73-82. doi: 10.1016/j.toxlet.2025.03.011. Epub 2025 Mar 28.
The organophosphorus pesticide chlorpyrifos (CPF) is widely utilized in agriculture to protect crops from pests and diseases. Concerns regarding its extensive use have emerged due to the substance's persistence, bioaccumulation, endocrine disruption, and associated toxicity, which may lead to various adverse reactions. In this study, 32 male C57BL/6 J mice were orally administered varying doses of CPF over a period of two weeks. Metabolic perturbations resulting from subacute exposure to CPF were assessed using LC-MS/MS-based untargeted metabolomics, alongside biochemical analysis and histopathological techniques. The 16S rRNA gene sequencing method was employed to evaluate changes in the gut microbial community within the cecal contents of mice exposed to CPF. In vivo studies have shown that CPF exposure induced dose-dependent damage and dysregulation of the intestinal microbiota in mouse colonic tissues. This was characterized by significant alterations in the gut microbiota, increased intestinal permeability and elevated levels of lipopolysaccharides. These changes may have compromised intestinal barrier function and facilitated the transfer of intestinal microbial metabolites and endotoxins to the liver, subsequently leading to liver injury. Collectively, this study elucidates a potential mechanism by which CPF triggers liver injury through alterations in the intestinal microbial community and increased intestinal permeability. These findings not only enhance our understanding of the toxicological effects of CPF but also contribute to the assessment of health risks associated with CPF exposure.
有机磷农药毒死蜱（CPF）在农业中被广泛用于保护作物免受病虫害侵害。由于该物质具有持久性、生物累积性、内分泌干扰性及相关毒性，可能导致各种不良反应，人们对其广泛使用产生了担忧。在本研究中，32只雄性C57BL/6 J小鼠在两周时间内口服了不同剂量的CPF。使用基于液相色谱-质谱联用（LC-MS/MS）的非靶向代谢组学技术，结合生化分析和组织病理学技术，评估了亚急性暴露于CPF所导致的代谢紊乱。采用16S rRNA基因测序方法评估暴露于CPF的小鼠盲肠内容物中肠道微生物群落的变化。体内研究表明，CPF暴露会导致小鼠结肠组织中肠道微生物群出现剂量依赖性损伤和失调现象。其特征表现为肠道微生物群显著改变、肠道通透性增加以及脂多糖水平升高。这些变化可能损害了肠道屏障功能，促进了肠道微生物代谢产物和内毒素向肝脏的转移，进而导致肝损伤。总体而言，本研究阐明了CPF通过改变肠道微生物群落和增加肠道通透性引发肝损伤的潜在机制。这些发现不仅增进了我们对CPF毒理学效应的理解，也有助于评估与CPF暴露相关的健康风险。
