Multifaceted Effects of Subchronic Exposure to Chlorfenapyr in Mice: Implications from Serum Metabolomics, Hepatic Oxidative Stress, and Intestinal Homeostasis

作者：Yabing Xiong, Xiaoran Ma, Bingying He, Jianwen Zhi, Xueke Liu, Peng Wang, Zhiqiang Zhou, Donghui Liu · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.3c09682 · 被引用次数：14 · 研究领域：Metabolomics and Mass Spectrometry Studies、Pharmacogenetics and Drug Metabolism、Vitamin C and Antioxidants Research

As chlorfenapyr is a commonly used insecticide in agriculture, the health risks of subchronic exposure to chlorfenapyr remained unclear. This study aimed to extensively probe the health risks from subchronic exposure to chlorfenapyr at the NOAEL and 10-fold NOAEL dose in mice. Through pathological and biochemical examinations, the body metabolism, hepatic toxicity, and intestinal homeostasis were systematically assessed. After 12 weeks, a 10-fold NOAEL dose of chlorfenapyr resulted in weight reduction, increased daily food intake, and blood lipid abnormalities. Concurrently, this dosage induced hepatotoxicity and amplified oxidative stress in hepatocytes, a finding further supported in HepG2 cells. Moreover, chlorfenapyr resulted in intestinal inflammation, evidenced by increased inflammatory factors ( IL-17a, IL-10, IL-1β, IL-6, IL-22 ), disrupted immune cells ( RORγt, Foxp3 ), and compromised intestinal barriers ( ZO-1 and occludin ). By contrast, the NOAEL dose presented less toxicity in most evaluations. Serum metabolomic analyses unveiled widespread disruptions in pathways related to hepatotoxicity and intestinal inflammation, including NF-κB signaling, Th cell differentiation, and bile acid metabolism. Microbiomic analysis showed an increase in Lactobacillus, a decrease in Muribaculaceae, and diminished anti-inflammatory microbes, which further propelled the inflammatory response and leaded to intestinal inflammation. These findings revealed the molecular mechanisms und...