{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:21:57Z","timestamp":1790785317818,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R21 AA 028521AA028521"],"award-info":[{"award-number":["R21 AA 028521AA028521"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The chronic\u2010plus\u2010binge model of ethanol consumption, where chronically (8\u2010week) ethanol\u2010fed mice are gavaged a single dose of ethanol (E8G1), is known to induce steatohepatitis in mice. However, how chronically ethanol\u2010fed mice respond to multiple binges of ethanol remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extended the E8G1 model to three gavages of ethanol (E8G3) spaced 24\u2009h apart, sacrificed each group 9\u00a0h after the final gavage, analyzed liver injury, and examined gene expression changes using microarray analyses in each group to identify mechanisms contributing to liver responses to binge ethanol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Surprisingly, E8G3 treatment induced lower levels of liver injury, steatosis, inflammation, and fibrosis as compared to mice after E8G1 treatment. Microarray analyses identified several pathways that may contribute to the reduced liver injury after E8G3 treatment compared to E8G1 treatment. The gene encoding cytochrome P450 2B10 (<jats:italic>Cyp2b10<\/jats:italic>) was one of the top upregulated genes in the E8G1 group and was further upregulated in the E8G3 group, but only moderately induced after chronic ethanol consumption, as confirmed by RT\u2010qPCR and western blot analyses. Genetic disruption of <jats:italic>Cyp2b10<\/jats:italic> worsened liver injury in E8G1 and E8G3 mice with higher blood ethanol levels compared to wild\u2010type control mice, while in vitro experiments revealed that CYP2b10 did not directly promote ethanol metabolism. Metabolomic analyses revealed significant differences in hepatic metabolites from E8G1\u2010treated <jats:italic>Cyp2b10<\/jats:italic> knockout and WT mice, and these metabolic alterations may contribute to the reduced liver injury in <jats:italic>Cyp2b10<\/jats:italic> knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hepatic <jats:italic>Cyp2b10<\/jats:italic> expression is highly induced after ethanol binge, and such upregulation reduces acute\u2010on\u2010chronic ethanol\u2010induced liver injury via the indirect modification of ethanol metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14954","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T04:49:00Z","timestamp":1665636540000},"page":"2163-2176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hepatic <scp>CYP2B10<\/scp> is highly induced by binge ethanol and contributes to acute\u2010on\u2010chronic alcohol\u2010induced liver injury"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9840-2013","authenticated-orcid":false,"given":"Bryan","family":"Mackowiak","sequence":"first","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health  Bethesda Maryland 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