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This research was designed to study two death pathways involved in ACRL\u2010induced hepatotoxicity and the modulating effect of RAPA on the resulting hepatic injury. Thirty\u2010six adult male rats were divided into three groups: control group, ACRL\u2010treated group (20\u2009mg\u2009kg\/day), and the last group co\u2010treated with ACRL plus RAPA (0.5\u00a0mg\u2009kg\/day). Drugs were administered for 21\u2009days via oral gavage. Blood samples were collected to assess alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Livers were dissected; parts were used for detection of superoxide dismutase (SOD) and malondialdehyde (MDA) tissue levels. Other parts were processed for hematoxylin and eosin, Masson's trichrome staining, immunostaining for microtubule\u2010associated proteins 1A\/1B light chain 3B (LC3), ubiquitin\u2010binding protein (p62), caspase\u20103, and receptor\u2010interacting protein kinase 1 (RIPK1). ACRL induced a significant elevation in ALT, AST, MDA levels, and reduction in the SOD level. ACRL also induced hepatocellular injury, fibrosis, and defective autophagy indicated by elevation of LC3 and p62 and increased p62\/LC3 ratio. Moreover, it increased the apoptotic (caspase\u20103) and necroptotic (RIPK1) markers expression. RAPA significantly reduced liver enzymes, oxidative stress, fibrosis, and improved liver histology. Moreover, RAPA decreased p62\/LC3 ratio indicated enhanced autophagy, and significantly reduced caspase\u20103 and RIPK1 expression. In conclusion, RAPA maintained autophagic activity which may save the hepatocytes from PCD and enhance cell viability.<\/jats:p>","DOI":"10.1002\/ar.24587","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T17:02:07Z","timestamp":1611334927000},"page":"1984-1998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Protective effect of rapamycin against acrylamide\u2010induced hepatotoxicity: The associations between autophagy, apoptosis, and necroptosis"],"prefix":"10.1002","volume":"304","author":[{"given":"Omnia S.","family":"Erfan","sequence":"first","affiliation":[{"name":"Anatomy and embryology department, Faculty of Medicine Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-3765","authenticated-orcid":false,"given":"Hany M. 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