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Chronic Arsenic Exposure Induces Neuroinflammation by Regulating the Nrf2/NLRP3 Inflammasome Signaling Pathway
Jianyu Qu1,2, Changyi Pi1, Ying Ma1
1Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, China.
Journal of Agricultural and Food Chemistry
|December 7, 2025
Summary
Chronic arsenic exposure damages brain cells by disrupting the Nrf2/NLRP3 inflammasome pathway, leading to oxidative stress and neuroinflammation. This study clarifies the mechanism behind arsenic-induced neurotoxicity.
Area of Science:
- Environmental toxicology
- Neuroscience
- Molecular biology
Background:
- Arsenic is a toxic metalloid that can cause neurotoxicity.
- The exact mechanisms of chronic arsenic exposure-induced brain damage are not fully understood.
Purpose of the Study:
- To investigate the effects of chronic sodium arsenite (NaAsO2) exposure on the brain.
- To elucidate the role of the Nrf2/NLRP3 inflammasome signaling pathway in arsenic-induced neurotoxicity.
Main Methods:
- Mice and SH-SY5Y cells were exposed to chronic NaAsO2.
- Levels of pro-inflammatory cytokines, oxidative stress markers, Nrf2 pathway proteins/mRNAs, and NLRP3 inflammasome proteins/mRNAs were measured.
- SH-SY5Y cells were pretreated with a Nrf2 activator (CBR-470-1) or a NLRP3 inhibitor (MCC950).
Main Results:
- Chronic NaAsO2 exposure damaged hippocampal neurons, increased pro-inflammatory cytokines, and caused oxidative stress.
- NaAsO2 exposure decreased Nrf2 signaling and increased NLRP3 inflammasome activation.
- CBR-470-1 pretreatment mitigated NaAsO2-induced damage by regulating the Nrf2/NLRP3 pathway.
- MCC950 pretreatment alleviated neuroinflammation by inhibiting NLRP3 inflammasome activation.
Conclusions:
- Chronic NaAsO2 exposure induces neurotoxicity via the Nrf2/NLRP3 inflammasome signaling pathway.
- Targeting this pathway may offer a strategy for preventing arsenic-induced neurotoxicity.
