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This study examined the potential ameliorative effects of obeticholic acid (OCA) and methyl ferulic acid (MFA) against arsenic trioxide (ATO)\u2010induced hepatic injury in rats, focusing on the pro\u2010fibrotic TGF\u2010\u03b2\/Smad3 and pro\u2010inflammatory MAPK pathways. Male Wistar rats received ATO orally at 7.5\u2009mg\/kg\/day from day 7 to day 21. Concurrently, OCA and MFA were received orally for 21 days, either alone or in combination, at doses of 10 and 100\u2009mg\/kg, respectively. The current findings revealed that ATO caused significant hepatic damage, as indicated by derangements in liver function tests and histological damage. Hepatotoxicity was marked by increased oxidative stress markers (NADPH oxidase 1, malondialdehyde, and nitric oxide), lowered antioxidant defenses (GSH, SOD), and elevated pro\u2010inflammatory signals (IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, and COX\u20102). ATO also activated the hepatic profibrotic (TGF\u2010\u03b2\/Smad3) and pro\u2010inflammatory MAPK cascades and suppressed the anti\u2010apoptotic protein Bcl\u20102. Treatment with OCA and\/or MFA significantly improved liver function and histopathology, restored antioxidant capacity, and decreased oxidative and inflammatory markers. They also inhibited activation of the pro\u2010fibrotic and pro\u2010inflammatory pathways and suppressed apoptosis. The combination of OCA and MFA exhibited the most pronounced hepatoprotective effects. In conclusion, OCA and MFA mitigate ATO\u2010induced hepatotoxicity through their antioxidant, anti\u2010inflammatory, and anti\u2010apoptotic mechanisms. Hence, these findings may pave the way for clinical investigation into their potential use as adjunct therapeutic agents in arsenic\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jbt.70711","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T21:03:21Z","timestamp":1769461401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Obeticholic Acid and Methyl Ferulic Acid Mitigate Arsenic Trioxide\u2010Induced Hepatotoxicity by Targeting Profibrotic and Proinflammatory Signaling"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-5917","authenticated-orcid":false,"given":"Souty M. 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