{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:13:07Z","timestamp":1747282387917,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2014,12,18]],"date-time":"2014-12-18T00:00:00Z","timestamp":1418860800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>]) plus clopidogrel under the stimulation of acid secretion in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8\u2009mg\/kg\/h), and the stomach was perfused with 25\u2009mmol\/L<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>at a rate of 0.4\u2009mL\/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30\u2009mg\/kg) was given p.o. 24\u2009h before the perfusion. Rebamipide (3\u201330\u2009mg\/kg) or other antiulcer drugs were given i.d. before the<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>perfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Slight gastric bleeding or damage was observed with the perfusion of<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>plus clopidogrel. Rebamipide had no effect on acid secretion, but dose\u2010dependently prevented gastric bleeding in response to<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by<jats:styled-content style=\"fixed-case\">ASA<\/jats:styled-content>under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12774","type":"journal-article","created":{"date-parts":[[2014,12,21]],"date-time":"2014-12-21T17:13:10Z","timestamp":1419181990000},"page":"37-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats"],"prefix":"10.1111","volume":"29","author":[{"given":"Koji","family":"Takeuchi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"},{"name":"General Incorporated Association Kyoto Research Center for Gastrointestinal Diseases Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misaki","family":"Itayama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kikuko","family":"Amagase","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chitose","family":"Izuhara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics Division of Pathological Sciences Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/bmj.308.6921.81","article-title":"Collaborative overview of randomised trials of antiplatelet therapy\u2010I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients","volume":"308","author":"Antiplatelet Trialists' Collaboration","year":"1994","journal-title":"BMJ"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_1","DOI":"10.1046\/j.1365-2036.2003.01693.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_1","DOI":"10.1111\/j.1365-2036.2006.02759.x"},{"key":"e_1_2_6_5_1","first-page":"1577","article-title":"Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case\u2010control study","volume":"169","author":"Hallas J","year":"2007","journal-title":"Ugeskr Laeger"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_1","DOI":"10.1007\/s11894-009-0071-x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_7_1","DOI":"10.1111\/j.1365-2036.2008.03904.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_8_1","DOI":"10.1111\/j.1538-7836.2006.02162.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_9_1","DOI":"10.1370\/afm.1269"},{"doi-asserted-by":"publisher","key":"e_1_2_6_10_1","DOI":"10.1172\/JCI20986"},{"key":"e_1_2_6_11_1","first-page":"333","article-title":"Aggravation by clopidogrel, an anti\u2010platelet drug, of HCl\/aspirin\u2010induced gastric bleeding and lesions in rats: prophylactic effect of rebamipide","volume":"38","author":"Izuhara C","year":"2010","journal-title":"Jpn. 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