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Res."],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The current study aims at repurposing the anti-arthritic drug diacerein (DCN) for the treatment of acetaminophen hepatotoxicity and investigating the potential underlying mechanisms. Mice were randomly divided into six groups receiving either no treatment (control group), 20\u00a0mg\/kg DCN <jats:italic>i.p<\/jats:italic>, 400\u00a0mg\/kg acetaminophen <jats:italic>i.p<\/jats:italic>, DCN 4\u00a0h before acetaminophen, DCN 2\u00a0h after acetaminophen, or 400\u00a0mg\/kg N-acetylcysteine (NAC) <jats:italic>i.p<\/jats:italic>, 2\u00a0h after acetaminophen. Biomarkers of liver dysfunction, oxidative stress, and apoptosis were assessed. Hepatic necroinflammatory changes were evaluated along with hepatic expression of NF-\u03baB and caspase-1. The levels of NLRP3, IL-1\u03b2, IL-4, MCP-1, and TNF-\u03b1 in the liver, as well as CYP2E1 mRNA expression, were measured. Diacerein significantly reduced biomarkers of liver dysfunction, oxidative stress, hepatocyte necrosis, and infiltration of neutrophils and macrophages whether administered 4\u00a0h before or 2\u00a0h after acetaminophen. Further, the effects were comparable to those of NAC. Diacerein also counteracted acetaminophen-induced hepatocellular apoptosis by increasing Bcl-2 and decreasing Bax and caspase-3 expression levels. Moreover, DCN normalized hepatic TNF-\u03b1 and significantly decreased NF-\u03baB p65 expression. Accordingly, DCN can prevent or reverse acetaminophen hepatotoxicity in mice, suggesting potential utility as a repurposed drug for clinical treatment.<\/jats:p>","DOI":"10.1007\/s12272-022-01373-7","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T15:34:48Z","timestamp":1646408088000},"page":"142-158","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Diacerein counteracts acetaminophen-induced hepatotoxicity in mice via targeting NLRP3\/caspase-1\/IL-1\u03b2 and IL-4\/MCP-1 signaling pathways"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-7483","authenticated-orcid":false,"given":"Mahmoud","family":"Elshal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa E.","family":"Abdelmageed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"1373_CR1","doi-asserted-by":"publisher","first-page":"110594","DOI":"10.1016\/j.biopha.2020.110594","volume":"131","author":"M Almezgagi","year":"2020","unstructured":"Almezgagi M, Zhang Y, Hezam K, Shamsan E, Gamah M, Al-Shaebi F, Abbas AB, Shoaib M, Saif B, Han Y, Jia R (2020) Diacerein: recent insight into pharmacological activities and molecular pathways. 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