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In this study, we found that Cd exposure significantly reduced cell viability, including the increased populations of apoptotic cells and caspase\u20103\/\u20107\/\u201012 activation in HepG2 cells. Mechanistically, Cd initiated oxidative stress via elevating reactive oxygen species (ROS) levels, leading to oxidative damage in HepG2 cells. Simultaneously, Cd exposure induced endoplasmic reticulum (ER) stress via activating the protein kinase RNA\u2010like ER kinase (PERK)\u2010C\/EBP homologous protein (CHOP) axis in HepG2 cells, and subsequently disturbed ER function as increased Ca<jats:sup>2+<\/jats:sup> releasing from ER lumen. Intriguingly, further study revealed that oxidative stress is closely related with ER stress, as pretreatment with ROS scavenger, N\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine (NAC) markedly reduced ER stress as well as protected ER function in Cd treated HepG2 cell. Collectively, these findings first revealed Cd exposure induced HepG2 cells death via a ROS\u2010mediated PERK\u2010CHOP\u2010related apoptotic signaling pathway, which provides a novel insight into the mechanisms of Cd\u2010induced hepatotoxicity. Furthermore, inhibitors for oxidative stress and ER stress might be considered as a new strategy to prevent or treat this disorder.<\/jats:p>","DOI":"10.1002\/tox.23866","type":"journal-article","created":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T17:30:02Z","timestamp":1686418202000},"page":"2271-2280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>ROS<\/scp>\u2010mediated <scp>PERK\u2010CHOP<\/scp> pathway plays an important role in cadmium\u2010induced <scp>HepG2<\/scp> cells apoptosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Cao","family":"Zhaohui","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School University of South China  Hengyang China"},{"name":"The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education University of 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