The role of nuclear factor erythroid 2-related factor 2(NRF2)in arsenic toxicity  

作　　者：Sara R.El-Mahrouk Mahmoud A.El-Ghiaty Ayman O.S.El-Kadi 

机构地区：[1]Faculty of Pharmacy and Pharmaceutical Sciences,University of Alberta,Edmonton,Alberta T6G 2E1,Canada [2]Faculty of Pharmacy,Tanta University,Tanta,Gharbia,Egypt

出　　处：《Journal of Environmental Sciences》2025年第4期632-644,共13页环境科学学报(英文版)

基　　金：supported by the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant[RGPIN 250139]to A.O.S.E.

摘　　要：Arsenic,a naturally occurring toxic element,manifests in various chemical forms and is widespread in the environment.Exposure to arsenic is a well-established risk factor for an elevated incidence of various cancers and chronic diseases.The crux of arsenic-mediated toxicity lies in its ability to induce oxidative stress,characterized by an unsettling imbalance between oxidants and antioxidants,accompanied by the rampant generation of reactive oxygen species and free radicals.In response to this oxidative turmoil,cells deploy their defensemechanisms,prominently featuring the redox-sensitive transcription factor known as nuclear factor erythroid 2-related factor 2(NRF2).NRF2 stands as a primary guardian against the oxidative harm wrought by arsenic.When oxidative stress activates NRF2,it orchestrates a symphony of downstream antioxidant genes,leading to the activation of pivotal antioxidant enzymes like glutathione-S-transferase,heme oxygenase-1,and NAD(P)H:quinone oxidoreductase 1.This comprehensive review embarks on the intricate and diverse ways by which various arsenicals influence the NRF2 antioxidant pathway and its downstream targets,shedding light on their roles in defending against arsenic exposure toxic effects.It offers valuable insights into targeting NRF2 as a strategy for safeguarding against or treating the harmful and carcinogenic consequences of arsenic exposure.

关 键 词：ARSENIC NRF2 KEAP1 NQO1 HMOX1 Oxidative stress 

分 类 号：R73[医药卫生—肿瘤]