{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:32:59Z","timestamp":1773235979044,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[1999,7,1]],"date-time":"1999-07-01T00:00:00Z","timestamp":930787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During investigations on the effect of caffeine on ibuprofen-induced gastric mucosal lesions in rats, we have found that caffeine (p.o.) inhibits the development of ibuprofen-induced gastric lesions in a dose-dependent manner (ED50 18.4mg kg\u22121). To investigate this protective effect of caffeine, we have studied the effect of caffeine on HCl-ethanol-induced gastric mucosal lesions with or without indomethacin pretreatment.<\/jats:p>\n               <jats:p>Caffeine inhibited the development of HCl-ethanol-induced gastric lesions with and without indomethacin pretreatment. These results indicate that caffeine did not act as a mild irritant but, on the contrary, had protective effects. We measured the gastric mucosal prostaglandin E2 (PGE2) concentrations and gastric mucosal blood flow, as representative protective factors for gastric mucosa. Caffeine did not affect the gastric mucosal PGE2 concentrations 4 h after administration of ibuprofen. However, topical administration of caffeine resulted in an increase in gastric mucosal blood flow, as measured by laser Doppler flowmetry. We investigated the gastric acid secretion and gastric mucosal myeloperoxidase activity as representative aggressive factors for gastric mucosa. When caffeine was administered intraduodenally in pylorus-ligated rats, gastric acid secretion decreased in a dose-dependent manner, with an ED50 of 44.9mg kg\u22121. Caffeine decreased ibuprofen-induced gastric myeloperoxidase activity in a dose-dependent manner, with an ED50 of 9.1mg kg\u22121.<\/jats:p>\n               <jats:p>These findings indicate that caffeine, at least in rats, may inhibit the development of acute gastric mucosal injury. The mechanisms underlying the protective actions of caffeine are unclear, but may be related in part to an increase in gastric mucosal blood flow and suppression of neutrophil activation.<\/jats:p>","DOI":"10.1211\/0022357991773014","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"817-824","source":"Crossref","is-referenced-by-count":12,"title":["Effect of Caffeine on Ibuprofen-induced Gastric Mucosal Damage in Rats"],"prefix":"10.1093","volume":"51","author":[{"given":"Rika","family":"Koyama","sequence":"first","affiliation":[{"name":"Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd , 1\u20138-14 Ikue, Asahi-ku, Osaka 535-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd , 1\u20138-14 Ikue, Asahi-ku, Osaka 535-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd , 1\u20138-14 Ikue, Asahi-ku, Osaka 535-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichi","family":"Nakatsugi","sequence":"additional","affiliation":[{"name":"Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd , 1\u20138-14 Ikue, Asahi-ku, Osaka 535-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masumi","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd , 1\u20138-14 Ikue, Asahi-ku, Osaka 535-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,7,1]]},"reference":[{"key":"2024103110045198500_cit1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/BF01782814","article-title":"Role of neutrophils in indomethacin-induced gastric mucosal lesions in rats","volume":"44","author":"Alican","year":"1995","journal-title":"Inflamm. Res."},{"key":"2024103110045198500_cit2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/BF02010727","article-title":"Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Physicochemical and biochemical factors involved","volume":"64","author":"Beck","year":"1990","journal-title":"Arch. Toxicol"},{"key":"2024103110045198500_cit3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF00506492","article-title":"Methylxanthines and intestinal drug absorption","volume":"292","author":"Beubler","year":"1976","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol"},{"key":"2024103110045198500_cit4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1056\/NEJM197510302931803","article-title":"Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine","volume":"293","author":"Cohen","year":"1975","journal-title":"N. Engl. J. Med."},{"key":"2024103110045198500_cit5","first-page":"101","article-title":"Gastric mucosal blood flow and resistance to injury","volume-title":"Advances in Ulcer Disease","author":"Guth","year":"1980"},{"key":"2024103110045198500_cit6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/0090-6980(85)90025-5","article-title":"Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2","volume":"30","author":"Kobayashi","year":"1985","journal-title":"Prostaglandins"},{"key":"2024103110045198500_cit7","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3181\/00379727-144-37731","article-title":"Caffeine-induced gastric secretion in rats","volume":"144","author":"Kowalewski","year":"1973","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"2024103110045198500_cit8","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/0016-5085(84)90202-6","article-title":"Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models","volume":"87","author":"Krawisz","year":"1984","journal-title":"Gastroenterology"},{"key":"2024103110045198500_cit9","first-page":"G337","article-title":"Endogenous gastric mucosal prostaglandins: their role in mucosal integrity","volume":"242","author":"Ligumsky","year":"1982","journal-title":"Am. J. Physiol"},{"key":"2024103110045198500_cit10","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1007\/BF01296001","article-title":"Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants","volume":"37","author":"Matsumoto","year":"1992","journal-title":"Dig. Dis. Sci."},{"key":"2024103110045198500_cit11","first-page":"G601","article-title":"Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms","volume":"245","author":"Miller","year":"1983","journal-title":"Am. J. Physiol"},{"key":"2024103110045198500_cit12","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0021-5198(19)52438-6","article-title":"Effect of polyamines on acidified ethanol-induced gastric lesions in rats","volume":"33","author":"Mizui","year":"1983","journal-title":"Jpn. J. Pharmacol"},{"key":"2024103110045198500_cit13","first-page":"1241","article-title":"Effects of caffeine on acute and chronic gastric lesions in rats","volume":"80","author":"Okabe","year":"1981","journal-title":"Gastroenterology"},{"key":"2024103110045198500_cit14","first-page":"941","article-title":"Effect of caffeine on blood flow in the gastric mucosa in the rat","volume":"29","author":"Ozturkcan","year":"1974","journal-title":"Therapie"},{"key":"2024103110045198500_cit15","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/0090-6980(80)90144-6","article-title":"Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica","volume":"20","author":"Powell","year":"1980","journal-title":"Prostaglandins"},{"key":"2024103110045198500_cit16","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/0016-5085(87)90972-3","article-title":"Effect of indomethacin on gastric mucosal prostaglandins in humans. Correlation with mucosal damage","volume":"92","author":"Redfern","year":"1987","journal-title":"Gastroenterology"},{"key":"2024103110045198500_cit17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/0016-5085(79)90002-7","article-title":"Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury","volume":"77","author":"Robert","year":"1979","journal-title":"Gastroenterology"},{"key":"2024103110045198500_cit18","first-page":"G113","article-title":"Mild irritants prevent gastric necrosis through \u201cadaptive cytoprotection\u201d mediated by prostaglandins","volume":"245","author":"Robert","year":"1983","journal-title":"Am. J. Physiol"},{"key":"2024103110045198500_cit19","first-page":"43","article-title":"Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action","volume":"45","author":"Sawynok","year":"1993","journal-title":"Pharmacol. Rev."},{"issue":"Suppl. 1","key":"2024103110045198500_cit20","first-page":"9","article-title":"Nonsteroidal anti-inflammatory drugs: how do they damage gastroduodenal mucosa? Dig","volume":"13","author":"Scarpignato","year":"1995","journal-title":"Dis"},{"key":"2024103110045198500_cit21","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1111\/j.2042-7158.1979.tb13677.x","article-title":"Effects of phenacetin, paracetamol and caffeine on the erosive activity of acetylsalicylic acid in the rat stomach: dose-response relationships, time course of erosion development and effects on acid secretion","volume":"31","author":"Seegers","year":"1979","journal-title":"J. Pharm. Pharmacol"},{"key":"2024103110045198500_cit22","first-page":"43","article-title":"A simple method for the uniform production of gastric ulceration in the rat","volume":"4","author":"Shay","year":"1945","journal-title":"Gastroenterology"},{"key":"2024103110045198500_cit23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF00503502","article-title":"Increased synthesis of adrenomedullary catecholamines induced by caffeine and theophylline","volume":"281","author":"Snider","year":"1974","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol"},{"key":"2024103110045198500_cit24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1159\/000200718","article-title":"Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats. Relation to gastric hypermotility","volume":"49","author":"Takeuchi","year":"1991","journal-title":"Digestion"},{"key":"2024103110045198500_cit25","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1440-1746.1997.tb00443.x","article-title":"Analysis of pathogenic elements involved in gastric lesions induced by non-steroidal anti-inflammatory drugs in rats","volume":"12","author":"Takeuchi","year":"1997","journal-title":"J. Gastroenterol. Hepatol"},{"key":"2024103110045198500_cit26","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/0041-008X(85)90348-5","article-title":"Effect of nicotine and caffeine pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats","volume":"79","author":"Tariq","year":"1985","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2024103110045198500_cit27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/BF01535735","article-title":"Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats","volume":"33","author":"Ueki","year":"1988","journal-title":"Dig. Dis. Sci."},{"key":"2024103110045198500_cit28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/BF02063956","article-title":"Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion in pylorus-ligated rat","volume":"40","author":"Wagner","year":"1995","journal-title":"Dig. Dis. Sci."},{"key":"2024103110045198500_cit29","first-page":"91","article-title":"Actions and interactions of endothelins, prostacyclin and nitric oxide in the gastric mucosa","volume":"44","author":"Whittle","year":"1993","journal-title":"J. Physiol. Pharmacol"},{"key":"2024103110045198500_cit30","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1254\/jjp.28.607","article-title":"Role of gastric motility in development of stress-induced gastric lesions of rats","volume":"28","author":"Yano","year":"1978","journal-title":"Jpn. J. Pharmacol"},{"key":"2024103110045198500_cit31","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1248\/bpb1978.5.485","article-title":"The etiology of caffeine-induced aggravation of gastric lesions in rats exposed to restraint plus water-immersion stress","volume":"5","author":"Yano","year":"1982","journal-title":"J. Pharmacobiodyn"},{"issue":"Suppl. 1","key":"2024103110045198500_cit32","first-page":"S73","article-title":"Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin","volume":"21","author":"Yoshida","year":"1995","journal-title":"J. Clin. Gastroenterol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1211%2F0022357991773014","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/51\/7\/817\/60262989\/0022357991773014.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/51\/7\/817\/60262989\/0022357991773014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T10:39:05Z","timestamp":1730371145000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/51\/7\/817\/6157306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7,1]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[1999,7,1]]},"published-print":{"date-parts":[[1999,7,1]]}},"URL":"https:\/\/doi.org\/10.1211\/0022357991773014","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1999,7]]},"published":{"date-parts":[[1999,7,1]]}}}