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To address these limitations, we synthesized curcumin derivatives and investigated the cytoprotective effects of a monocarbonyl analog, GO-Y015. GO-Y015 exhibited cytotoxicity comparable to curcumin at concentrations below 8\u00a0\u00b5M but significantly reduced As(III)-induced cytotoxicity. Pretreatment with GO-Y015 markedly improved cell viability under cytotoxic As(III) exposure, whereas curcumin showed minimal protective effects. Mechanistically, GO-Y015 induced robust Nrf2 activation in a concentration- and time-dependent manner, resulting in increased expression of downstream targets, including HO-1, GCLC, and MRP2. Pharmacological inhibition of Nrf2 (ML385), GSH synthesis (BSO), or MRP transporters (MK571) abolished the cytoprotective effects, indicating dependence on the Nrf2\u2013GSH\u2013MRP axis. Furthermore, ICP-MS analysis demonstrated that GO-Y015 significantly reduced intracellular arsenic accumulation after 2\u00a0h exposure. These findings indicate that GO-Y015 enhances arsenic detoxification and reduces cytotoxicity by promoting GSH-dependent conjugation and MRP-mediated efflux.<\/jats:p>","DOI":"10.1038\/s41598-026-49334-0","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T07:33:05Z","timestamp":1776497585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nrf2 activation by the monocarbonyl curcumin derivative GO-Y015 confers cellular protection against arsenite toxicity by reducing intracellular arsenic levels"],"prefix":"10.1038","volume":"16","author":[{"given":"Md. 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