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  3. Mechanisms of colon toxicity induced by long-term perfluorooctanoic acid exposure in mice

Mechanisms of colon toxicity induced by long-term perfluorooctanoic acid exposure in mice

  • Ecotoxicol Environ Saf. 2024 Sep 1:282:116762. doi: 10.1016/j.ecoenv.2024.116762.
Xiannan Meng 1,  Wei Li 2,  Yongjing Qian 3,  Xiaojing Cai 4,  Jianfeng Wei 5,  Ling Zhang 6
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: mengxiann@xzhmu.edu.cn.
  • 2 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: pearweier@163.com.
  • 3 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: 2749822202@qq.com.
  • 4 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: 3399467588@qq.com.
  • 5 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: wjf@xzhmu.edu.cn.
  • 6 Department of Histology and Embryology, School of Basic Medical Sciences, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: zhanglxy@xzhmu.edu.cn.
PMID: 39047366 DOI: 10.1016/j.ecoenv.2024.116762
Abstract

Perfluorooctanoic acid (PFOA), a persistent organic pollutant known for its chemical stability, is widely dispersed in the environment, posing significant health risks to mammals through various exposure routes such as ingestion, inhalation, and dermal contact. In this study, mice were exposed to PFOA (0, 0.2, 2 mg/L) through drinking water for 180 days to investigate its toxic effects on the colon. We identified differentially expressed genes through RNA Sequencing and validated the impact of PFOA on the expression of these genes in colon tissue. Our findings revealed that long-term exposure to PFOA caused inflammatory bowel disease (IBD)-like damage to the mouse colon. We found PFOA could induce damage to the intestinal barrier. Inhibition of the Wnt signaling pathway following PFOA exposure results in impaired stem cell function in the colon of mice. Furthermore, PFOA activated the PPAR signaling pathway, disrupting cellular lipid metabolism in colon tissues. Additionally, PFOA induced inflammatory responses in colon tissue, facilitating NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation and cell Apoptosis. This study offers a thorough understanding of the mechanisms responsible for the damage to mouse colon tissue resulting from long-term exposure to PFOA.

Keywords

Inflammation; Intestinal barrier; Intestinal stem cells; PFOA.

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