2. Academic Validation
  3. Chronic Arsenic Exposure Induces Neuroinflammation by Regulating the Nrf2/NLRP3 Inflammasome Signaling Pathway

Chronic Arsenic Exposure Induces Neuroinflammation by Regulating the Nrf2/NLRP3 Inflammasome Signaling Pathway

  • J Agric Food Chem. 2025 Dec 17;73(50):31853-31864. doi: 10.1021/acs.jafc.5c12523.
Jianyu Qu 1 2,  Changyi Pi 1,  Ying Ma 1,  Xin Jiang 1,  Xin Sheng 1,  Yuanbin Wang 1,  Jine Yi 1,  Jing Wu 1,  Ji Wang 1,  Lixin Wen 1,  Shuiping Liu 1
Affiliations

Affiliations

  • 1 Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, China.
  • 2 College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China.
PMID: 41353618 DOI: 10.1021/acs.jafc.5c12523
Abstract

Arsenic, an environmental toxic metalloid, readily crosses the blood-brain barrier to induce neurotoxicity, but the mechanism of chronic arsenic exposure-induced brain damage remains unclear. In this study, results demonstrated that chronic NaAsO2 exposure damaged hippocampal neurons, increased the production of pro-inflammatory cytokines, and caused oxidative stress in mice and SH-SY5Y cells. Besides, chronic NaAsO2 exposure decreased the levels of the Nrf2 signaling pathway-related mRNA/protein while increasing the levels of the NLRP3 inflammasome-related mRNA/protein. CBR-470-1 (a Nrf2 activator) pretreatment mitigated NaAsO2 exposure-induced oxidative stress and neuroinflammation by regulating the Nrf2/NLRP3 inflammasome signaling pathway in SH-SY5Y cells. Meanwhile, MCC950 (a NLRP3 Inhibitor) pretreatment alleviated NaAsO2-induced neuroinflammation by inhibiting the NLRP3 inflammasome activation without affecting the Nrf2 signaling pathway in SH-SY5Y cells. In conclusion, chronic NaAsO2 exposure induced oxidative stress and neuroinflammation in mice and SH-SY5Y cells through regulation of the Nrf2/NLRP3 inflammasome signaling pathway, which provides a theoretical basis for preventing chronic arsenic exposure-induced neurotoxicity.

Keywords

NLRP3 inflammasome; Nrf2; chronic arsenic exposure; neuroinflammation; oxidative stress.

Figures
Products