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The current study focused on the potential protective capacity of melatonin against arsenic\u2010induced hepatotoxicity. Thirty\u2010six male Wistar rats were allocated into control, arsenic (15\u2009mg\/kg; orally), arsenic (15\u2009mg\/kg) plus melatonin (10, 20, and 30\u2009mg\/kg; intraperitoneally), and melatonin alone (30\u2009mg\/kg) groups for 28 days. After the treatment period, the serum sample was separated to measure liver enzymes (AST and ALT). The liver tissue was removed and then histological alterations, oxidative stress markers, antioxidant capacity, the levels of Nrf2 and HO\u20101, apoptosis (Bcl\u20102, survivin, Mcl1, Bax, and caspase\u20103), and autophagy (Sirt1, Beclin\u20101, and LC3 II\/I ratio) proteins, as well as the expression level of miR\u201034a, were evaluated on this tissue. Arsenic exposure resulted in the enhancement of serum AST, ALT, and substantial histological damage in the liver. Increased levels of malondialdehyde, a lipid peroxidation marker, and decreased levels of physiological antioxidants including glutathione, superoxide dismutase, and catalase were indicators of arsenic\u2010induced oxidative damage. The levels of Nrf2, HO\u20101, and antiapoptotic proteins diminished, while proapoptotic and autophagy proteins were elevated in the arsenic group concomitant with a low level of hepatic miR\u201034a. The co\u2010treatment of melatonin and arsenic reversed the changes caused by arsenic. These findings showed that melatonin reduced the hepatic damage induced by arsenic due to its antioxidant and antiapoptotic properties as well as its regulatory effect on the miR\u201034a\/Sirt1\/autophagy pathway.<\/jats:p>","DOI":"10.1002\/jbt.23635","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T02:53:40Z","timestamp":1704336820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Melatonin attenuates liver injury in arsenic\u2010treated rats: The potential role of the Nrf2\/HO\u20101, apoptosis, and miR\u201034a\/Sirt1\/autophagy pathways"],"prefix":"10.1002","volume":"38","author":[{"given":"Samira","family":"Barangi","sequence":"first","affiliation":[{"name":"Student Research Committee Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Pharmaceutical Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-2343","authenticated-orcid":false,"given":"Soghra","family":"Mehri","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Moosavi","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Faculty of Veterinary Medicine Ferdowsi University of Mashhad  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Yarmohammadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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