{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T11:45:31Z","timestamp":1759664731062,"version":"3.30.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6970,"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":[[1996,8]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>It has been shown recently that inactivation of Kupffer cells prevents free radical formation and early alcohol\u2013induced liver injury, and that hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells is likely involved in the mechanism. Calcium is essential for the activation of Kupffer cells, which contain L\u2013type voltage\u2013dependent Ca2+ channels. Therefore, the purpose of this study was to determine whether a Ca2+ channel blocker, nimodipine, prevents early alcohol\u2013induced liver injury<\/jats:bold>\n                                 <jats:bold>\n                                    in vivo\n                                 <\/jats:bold>\n                                 <jats:bold>and to evaluate its effect on intracellular calcium ([Ca2+]i) in Kupffer cells<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>. Male Wistar rats were exposed to ethanol (10\u201312 g\/kg\/d) continuously for up to 4 weeks via intragastric feeding using an enteral model developed by Tsukamoto and French. In this model, ethanol causes steatosis, necrosis, and inflammation in only a few weeks. In the experimental group, nimodipine (10 mg\/kg\/d) was added to the diet and was shielded from direct light. Nimodipine had no effect on body weight over a 4\u2013week treatment period, nor were mean ethanol concentrations or their cyclic pattern in urine affected. The mean urine ethanol values were 154 \u00b1 11 mg\/dL in ethanol\u2013fed and 144 \u00b1 38 mg\/dL in ethanol + nimodipine\u2013fed rats. After 4 weeks, serum aspartate transaminase (AST) levels were elevated in ethanol\u2013treated rats to 183 \u00b1 78 U\/L. In contrast, values only reached 101 \u00b1 9 U\/L in rats given nimodipine + ethanol\u2013values which were significantly lower. Steatosis and necrosis assessed histologically were also reduced significantly by nimodipine. Nimodipine (10 micrograms\/kg) also blocked the swift increase in alcohol metabolism and elevated oxygen consumption in perfused livers from rats treated with alcohol in vivo. Further, in cultured Kupffer cells, nimodipine (1 mumol\/L) largely prevented the elevation in [Ca2+]i caused by lipopolysaccharide (LPS) (LPS, 200 \u00b1 11 nmol\/L; LPS + nimodipine, 94 \u00b1 31 nmol\/L;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; .05). These results indicate that nimodipine prevents alcoholic hepatitis, possibly by inhibition of endotoxin\u2013mediated Kupffer cell activation.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510240217","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T00:08:48Z","timestamp":1100218128000},"page":"391-397","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":46,"title":["Nimodipine, A Dihydropyridine\u2013Type Calcium Channel Blocker, Prevents Alcoholic Hepatitis Caused by Chronic Intragastric Ethanol Exposure in the Rat"],"prefix":"10.1097","volume":"24","author":[{"given":"Y","family":"Iimuro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Ikejima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M L","family":"Rose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B U","family":"Bradford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R 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\/10.1002%2Fhep.510240217","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199608000-00017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:14:54Z","timestamp":1733051694000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199608000-00017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,8]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1996]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510240217","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[1996,8]]}}}