{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:12:34Z","timestamp":1780657954096,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T00:00:00Z","timestamp":1527033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI Grant","award":["#25460879"],"award-info":[{"award-number":["#25460879"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI Grant","award":["#16K09223"],"award-info":[{"award-number":["#16K09223"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Alcohol dehydrogenases (ADHs) 1 and 3 are responsible for systemic alcohol metabolism. The current study investigated the contribution of liver ADH1 and ADH3 to the metabolic pharmacokinetics of chronic alcohol consumption (CAC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 9\u2010week\u2010old male mice of different ADH genotypes (wild\u2010type [WT], <jats:italic>Adh1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>, and <jats:italic>Adh3<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) were administered with 10% ethanol solution for 1\u00a0month, followed by acute ethanol administration (4.0\u00a0g\/kg). The alcohol elimination rate (AER), area under the blood alcohol concentration curve (AUC), and the maximum blood alcohol concentration (C<jats:sub>max<\/jats:sub>) were calculated. The liver content, activity, and mRNA levels of ADH were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic alcohol consumption increased the AER and reduced the AUC in all ADH genotypes. The increased ADH1 content was correlated with AER in WT mice but not in the <jats:italic>Adh3<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Similarly, the increased ADH3 content was also correlated with AER in both WT and <jats:italic>Adh1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. The C<jats:sub>max<\/jats:sub> was significantly higher in <jats:italic>Adh3<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> control mice than in WT control mice. It decreased in the <jats:italic>Adh1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice by CAC along with an increase in the ADH3 content.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alcohol dehydrogenases 1 and 3 would accomplish the pharmacokinetic adaptation to CAC in the early period. ADH1 contributes to the metabolic pharmacokinetics of CAC with a decrease in AUC in conjunction with an increase of AER by increasing the enzyme content in the presence of ADH3. ADH3 also contributes to a decrease in AUC in conjunction with not only an increase in AER but also a decrease in C<jats:sub>max<\/jats:sub> by increasing the enzyme content.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14260","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T08:42:24Z","timestamp":1523954544000},"page":"1912-1919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Metabolic pharmacokinetics of early chronic alcohol consumption mediated by liver alcohol dehydrogenases 1 and 3 in mice"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-4802","authenticated-orcid":false,"given":"Takahisa","family":"Okuda","sequence":"first","affiliation":[{"name":"Department of Legal Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Haseba","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Nippon Medical School  Tokyo Japan"},{"name":"Department of Legal Medicine Kanagawa Dental University  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Katsuyama","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyo","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Science Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Science Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youkichi","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60009-X"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000324289"},{"key":"e_1_2_5_4_1","first-page":"220","article-title":"Relationships between nutrition, alcohol use, and liver disease","volume":"27","author":"Lieber CS","year":"2003","journal-title":"Alcohol Res. 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