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

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.