2. Academic Validation
  3. Fluxapyroxad induces chronic colonic inflammation via inhibiting intestinal aryl hydrocarbon receptors in mice

Fluxapyroxad induces chronic colonic inflammation via inhibiting intestinal aryl hydrocarbon receptors in mice

  • Sci Total Environ. 2025 Apr 10:973:179134. doi: 10.1016/j.scitotenv.2025.179134.
Yue Cao 1,  Shouchun Xiao 2,  Yaofeng Fang 3,  Jiaxing Yang 4,  Zeyu Hu 3,  Hongjun Zhang 5,  Xueke Liu 6,  Donghui Liu 7,  Zhiqiang Zhou 8,  Peng Wang 9
Affiliations

Affiliations

  • 1 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: yue.cao@cau.edu.cn.
  • 2 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: xiaosc0313@163.com.
  • 3 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China.
  • 4 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: S20233102308@cau.edu.cn.
  • 5 Institute for the Control of Agrochemicals, Ministry of Agriculture and Rural Affairs, China, No. 22 Maizidian Street, Chaoyang, Beijing 100125, PR China. Electronic address: zhanghongjun@agri.gov.cn.
  • 6 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: liuxueke@cau.edu.cn.
  • 7 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: liudh@cau.edu.cn.
  • 8 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: zqzhou@cau.edu.cn.
  • 9 Department of Applied Chemistry, College of Science, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100193, PR China. Electronic address: wangpeng@cau.edu.cn.
PMID: 40112552 DOI: 10.1016/j.scitotenv.2025.179134
Abstract

Fluxapyroxad, the most extensively utilized Succinate Dehydrogenase Inhibitor (SDHI) fungicide, lacks comprehensive research on potential risks associated with chronic toxicity. To investigate its effects on chronic colonic inflammation and elucidate the underlying mechanisms, a mouse model was employed to assess oral exposure to fluxapyroxad at no observed adverse effect level (NOEL) for 13 weeks, in vitro and in silico models were utilized as well. The results revealed reduced body weight gain, colon length reduction, crypt damage, goblet cell loss in the colon, impaired intestinal barrier integrity, and an elevation of proinflammatory cytokines, including IL-6, IL-1β, and TNF-α following fluxapyroxad exposure in mice. These findings suggested that fluxapyroxad induced chronic colonic inflammation. Furthermore, fluxapyroxad decreased interleukin 22 levels and Antibacterial peptide secretion by inhibiting Aryl hydrocarbon receptors (AhR) activation, which was confirmed in vitro experiments. Molecular docking analysis indicated that fluxapyroxad spontaneously formed halogen bonds and bound hydrophobic interactions with AhR, which might act as an AhR inhibitor. These results indicated that AhR inhibition may represent one of the primary mechanisms for chronic colonic inflammation induced by fluxapyroxad exposure. This study shed light on the association between low acute pesticide exposure to fluxapyroxad and chronic colonic inflammation development while contributing to pesticide safety assessment.

Keywords

Aryl hydrocarbon receptors; Chronic colonic inflammation; Fluxapyroxad; Intestinal barrier integrity.

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