{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:58:43Z","timestamp":1792681123253,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Prevention of liver failure arising from accidental or deliberate paracetamol (acetaminophen [APAP]) overdose remains a vexed health problem despite well\u2010publicized guidelines for its early detection and treatment. It is recognized that the gut may aggravate liver pathology, via the gut\u2013liver axis. The main aim of this study was to assess the role of the colon in APAP\u2010induced liver toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver necrosis and colitis were studied following sublethal doses of APAP administered intraperitoneally to C57Bl\/6 wild\u2010type (WT) mice, as well as to C57Bl\/6 <jats:italic>Winnie<\/jats:italic> mice, which develop a spontaneous colitis caused by a SNP in <jats:italic>Muc2<\/jats:italic>, and WT mice with acute DSS\u2010induced colitis. Repeated APAP exposure was studied in WT and Rag1 ko mice that lack mature T and B lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>APAP overdose resulted in significant colonic injury in WT mice (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), which resolved by 24\u00a0h. Underlying colitis was not associated with liver necrosis, but colitis exacerbated APAP\u2010induced liver injury and extended APAP\u2010colonic injury. Prior APAP exposure exacerbated both APAP\u2010liver and APAP\u2010colonic injury more so in WT than Rag1 ko mice. APAP impaired barrier function with increased intestinal permeability and associated bacterial translocation to the liver and spleen in mice with the <jats:italic>Winnie<\/jats:italic> phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study identifies novel roles for APAP in causing colitis, the amplification of APAP\u2010liver toxicity where there is underlying colitis, and involvement of immune memory in APAP\u2010toxicity. The latter could be key for decoding the poorly understood but important clinical entity of chronic APAP liver failure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16102","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:55:16Z","timestamp":1672840516000},"page":"609-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gut inflammation and adaptive immunity amplify acetaminophen toxicity in bowel and liver"],"prefix":"10.1111","volume":"38","author":[{"given":"Saleh Y","family":"Alabbas","sequence":"first","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabina","family":"Giri","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia","family":"Oancea","sequence":"additional","affiliation":[{"name":"Medical School University of Queensland  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Davies","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Schreibner","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-9848","authenticated-orcid":false,"given":"Timothy H","family":"Florin","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-7672","authenticated-orcid":false,"given":"Jakob","family":"Begun","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute  South Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ncp.10459"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03765.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.3.4.269"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.05.011"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215570992"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00878.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.023"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0011-z"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.003"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020395"},{"key":"e_1_2_6_12_1","article-title":"Gut\u2010liver axis: how do gut bacteria influence the liver?","volume":"6","author":"Konturek PC","year":"2018","journal-title":"Med. 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