Sodium arsenite induces spatial learning and memory impairment associated with oxidative stress and activates the Nrf2/PPARγ pathway against oxidative injury in mice hippocampus.

Autor:	Xiong L; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China., Huang J; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China., Gao Y; Department of rehabilitation medicine, School of Rehabilitation, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Gao Y; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China., Wu C; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China., He S; School of Public Health and Health Management, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Zou L; School of Public Health and Health Management, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Yang D; School of Public Health and Health Management, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Han Y; School of Public Health and Health Management, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Yuan Q; School of Public Health and Health Management, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, Jiangxi, China., Zheng Z; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China., Hu G; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Number 1 Yixueyuan Road, Ganzhou 341000, China.
Jazyk:	angličtina
Zdroj:	Toxicology research [Toxicol Res (Camb)] 2021 Feb 17; Vol. 10 (2), pp. 277-283. Date of Electronic Publication: 2021 Feb 17 (Print Publication: 2021).
DOI:	10.1093/toxres/tfab007
Abstrakt:	Arsenic (As) is a ubiquitous environmental and industrial toxin with known correlates of oxidative stress and cognitive deficits in the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that represents a central cellular antioxidant defense mechanism and transcribes many antioxidant genes. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a well-known nuclear receptor to regulate lipid metabolism in many tissues, and it has been also associated with the control of oxidative stress, neuronal death, neurogenesis and differentiation. The role of Nrf2 and PPARγ in As-induced neurotoxicity is still debated. The present study was designed to investigate the neurobehavioral toxic effect of sub-chronic and middle-dose sodium arsenite exposure in mice hippocampus, as well as the response of Nrf2/PPARγ expression and influence on protein expression levels of their downstream antioxidant genes. Our results showed that mice treated with intraperitoneal injection of sodium arsenite (50 mg/kg body wt.) twice a week for 7 weeks resulted in increased generation of reactive oxygen species and impairment of spatial cognitive function. The present study also found a positive association between Nrf2/PPARγ expression in hippocampus of mice, and activation of antioxidant defenses by the evidently upregulated expression of their downstream genes, including superoxide dismutase, heme oxygenase-1 and glutathione peroxidase-3. Therefore, our findings were helpful for further understanding the role of Nrf2/PPARγ feedback loop in As-induced neurobehavioral toxicity. (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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