{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:25:21Z","timestamp":1762874721154,"version":"3.37.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5022,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Chronic alcohol administration increases gut-derived endotoxin in the portal blood, which activates Kupffer cells through nuclear factor \u03baB (NF-\u03baB) to produce toxic mediators such as proinflammatory cytokines, leading to liver injury. Therefore, a long-term intragastric ethanol feeding protocol was used here to test the hypothesis that NF-\u03baB inhibition would prevent early alcohol-induced liver injury. Adenoviral vectors encoding either the transgene for I\u03baB superrepressor (AdI\u03baB-SR) or the bacterial \u03b2-galactosidase reporter gene (AdlacZ) were administered intravenously to Wistar rats. Animals were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin (control) for 3 weeks. There was no significant difference in mean urine alcohol concentrations between the groups fed ethanol. I\u03baB-SR expression was increased for up to 2 weeks after injection, but was undetectable at 3 weeks. NF-\u03baB activation was increased by ethanol and associated with up-regulation of tumor necrosis factor \u03b1 (TNF-\u03b1). These increases were blunted significantly up to 2 weeks by AdI\u03baB-SR. Dietary alcohol significantly increased liver to body weight ratios and serum alanine transaminase (ALT) levels in AdlacZ-treated animals, effects that were blunted significantly in AdI\u03baB-SR-treated rats. Ethanol caused severe steatosis, inflammation, and focal necrosis in AdlacZ-treated animals. These pathologic changes were significantly decreased by AdI\u03baB-SR. The protective effects of I\u03baB-SR were significant 2 weeks after injection, but were lost at 3 weeks when I\u03baB-SR was no longer expressed. Ethanol increased 4-hydroxynonenal as a maker of oxidative stress in both AdlacZ and AdI\u03baB groups. These data support the hypothesis that NF-\u03baB inhibition prevents early alcohol-induced liver injury even in the presence of oxidative stress.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2001.29400","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T03:46:10Z","timestamp":1030247170000},"page":"1149-1157","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":70,"title":["Delivery of I\u03baB superrepressor gene with adenovirus reduces early alcohol-induced liver injury in rats"],"prefix":"10.1097","volume":"34","author":[{"given":"Takehiko","family":"Uesugi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Froh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin E.","family":"Arteel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blair U.","family":"Bradford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"G\u00e1bele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Wheeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald G.","family":"Thurman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2001.29400","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200112000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T15:39:14Z","timestamp":1738942754000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200112000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2001.29400","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[2001,12]]}}}