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

• Published in: Journal of agricultural and food chemistry 2024-04, Vol.72 (13), p.7423-7437
• Main Authors: Xiong, Yabing, Ma, Xiaoran, He, Bingying, Zhi, Jianwen, Liu, Xueke, Wang, Peng, Zhou, Zhiqiang, Liu, Donghui
• Format: Article
• Language: English
• Subjects: bile acids; blood lipids; blood serum; cell differentiation; chlorfenapyr; food chemistry; food intake; Food Safety and Toxicology; hepatocytes; hepatotoxicity; homeostasis; inflammation; interleukin-10; interleukin-17; interleukin-6; intestinal microorganisms; intestines; Lactobacillus; metabolism; metabolomics; occludins; oxidative stress; subchronic exposure; weight loss
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.3c09682

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 underlying chlorfenapyr-induced hepatotoxicity and intestinal inflammation, highlighting the significant role of the gut microbiota.