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Hexavalent chromium [Cr(VI)], a common environmental pollutant related to liver injury, likely leads to premature senescence in L02 hepatocytes. However, the underlying mechanisms regarding hepatocyte premature senility in Cr(VI) exposure remain poorly understood. In this study, we found that chronic exposure of L02 hepatocytes to Cr(VI) led to premature senescence characterized by increased\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010galactosidase activity, senescence\u2010associated heterochromatin foci, G1 phase arrest, and decreased cell proliferation. Additionally, Cr(VI)\u2010induced senescent L02 hepatocytes showed upregulated inflammation\u2010related factors, such as IL\u20106 and fibroblast growth factor 23 (FGF23), which also exhibited reactive oxygen species (ROS) accumulation derived from mitochondria accompanied with increased concentration of intracellular calcium ions (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) and activity of nuclear factor kappa B (NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B). Of note is that ROS inhibition by N\u2010acetyl\u2010Lcysteine pretreatment not only alleviated Cr(VI)\u2010induced premature senescence but also reduced the elevated intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , activated NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B, and secretion of IL\u20106\/FGF23. Intriguingly, the toxic effect of Cr(VI) upon premature senescence of L02 hepatocytes and increased levels of IL\u20106\/FGF23 could be partially reversed by the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    chelator BAPTA\u2010AM pretreatment. Furthermore, by utilizing the NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B inhibitor pyrrolidine dithiocarbamate (PDTC), we confirmed that NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B mediated IL\u20106\/FGF23 to regulate the Cr(VI)\u2010induced L02 hepatocyte premature senescence, whilst the concentration of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    was not influenced by PDTC. To the best of our knowledge, our data reports for the first time the role of ROS\u2010Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B signaling pathway in Cr(VI)\u2010induced premature senescence. Our results collectively shed light on further exploration of innovative intervention strategies and treatment targeting Cr(VI)\u2010induced chronic liver damage related to premature senescence.\n                  <\/jats:p>","DOI":"10.1155\/2022\/7295224","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T00:20:07Z","timestamp":1645230007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Regulation of Cr(VI)\u2010Induced Premature Senescence in L02 Hepatocytes by ROS\u2010Ca\n                    <sup>2+<\/sup>\n                    \u2010NF\u2010\n                    <i>\u03ba<\/i>\n                    B 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