{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T20:05:44Z","timestamp":1765656344930,"version":"3.48.0"},"reference-count":29,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1988,7]]},"abstract":"<jats:p>Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism.<\/jats:p>","DOI":"10.1136\/gut.29.7.894","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"894-902","source":"Crossref","is-referenced-by-count":39,"title":["Epidermal growth factor (EGF) in the gastroprotective and ulcer healing actions of colloidal bismuth subcitrate (De-Nol) in rats."],"prefix":"10.1136","volume":"29","author":[{"given":"S J","family":"Konturek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Dembinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z","family":"Warzecha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Bielanski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Brzozowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Drozdowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1988,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1136\/gut.28.2.201","article-title":"Gastroprotection by colloidal bismuth subcitrate (DE-NOL) and sucralfate. 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Arch Int Pharmacodyn 1987; 286: 308-19.","journal-title":"Arch Int Pharmacodyn"},{"key":"ref_3","first-page":"329","article-title":"Randomized open controlled trial of colloidal bismuth subcitrate tablets and cimetidine in the treatment of duodenal ulcer","volume-title":"Gut","volume":"21","author":"Vantrappen, G.; Rutgeerts, P.; Broekart, L.; Janssens, J.","year":"1980","unstructured":"Vantrappen G, Rutgeerts P, Broekart L, Janssens J. Randomized open controlled trial of colloidal bismuth subcitrate tablets and cimetidine in the treatment of duodenal ulcer. Gut 1980; 21: 329-53."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000198690","article-title":"Cimetidine and colloidal bismuth in treatment of chronic duodenal ulcer","volume":"23","author":"Kang, J.Y.; Piper, D.W.","year":"1982","unstructured":"Kang JY, Piper DW. Cimetidine and colloidal bismuth in treatment of chronic duodenal ulcer. 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Scand J Gastroenterol 1982; suppl 80: 17: 17-21.","journal-title":"Scand J Gastroenterol"},{"issue":"14","key":"ref_9","first-page":"48","article-title":"Does the duodenal cell ever return to normal? A comparison between treatment with cimetidine and DE-NOL","volume":"54","author":"Moshal, M.G.; Gregory, M.A.; Pillay, C.; Spitaels, J.M.","year":"1979","unstructured":"Moshal MG, Gregory MA, Pillay C, Spitaels JM. Does the duodenal cell ever return to normal? A comparison between treatment with cimetidine and DE-NOL. Scand J Gastroenterol 1979; suppl 54: 14: 48-51.","journal-title":"Scand J Gastroenterol"},{"key":"ref_10","first-page":"83","article-title":"Epidermal growth factor-like material rat submandibular gland","volume":"156","author":"Gresik, E.W.; Van der Noen, H.; Barka, T.","year":"1979","unstructured":"Gresik EW, Van der Noen H, Barka T. Epidermal growth factor-like material rat submandibular gland. Am JAnat 1979; 156: 83-9.","journal-title":"Am JAnat"},{"key":"ref_11","first-page":"1225","article-title":"Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands","volume-title":"Gut","volume":"25","author":"Kirkegaard, P.; Skov Olsen, P.; Nexo, E.; Holst, T.J.; Poulsen, S.S.","year":"1984","unstructured":"Kirkegaard P, Skov Olsen P, Nexo E, Holst TJ, Poulsen SS. Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands. Gut 1984; 25: 1225-9."},{"key":"ref_12","first-page":"438","article-title":"Gastric cytoprotection by epidermal growth factor. Role of endogenous prostaglandins","volume-title":"and DNA synthesis. Gastroenterology 1981; 81","author":"Konturek, S.J.; Radecki, T.; Brzozowski, T.","unstructured":"Konturek SJ, Radecki T, Brzozowski T, et al. Gastric cytoprotection by epidermal growth factor. 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Gastroenterology 1979; 76: 327-34.","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0014-5793(80)81125-2","article-title":"Demonstration of specific receptors for EGF-urogastrone in isolated rat intestinal epithelial cells","volume":"114","author":"Forgue-Lafitte, M.-E.; Labrthe, M.; Chamblier, M.-C.; Moody, A.J.; Rosselin, G.","year":"1980","unstructured":"Forgue-Lafitte M-E, Labrthe M, Chamblier M-C, Moody AJ, Rosselin G. Demonstration of specific receptors for EGF-urogastrone in isolated rat intestinal epithelial cells. FEBS Lett 1980; 114: 243-6.","journal-title":"FEBS Lett"},{"key":"ref_25","first-page":"776","article-title":"Control of a cell surface major glycoprotein by epidermal growth factor","author":"Chen, L.B.; Gudor, R.C.; Sun, T.-T.; Chen, A.B.; Mosesson, M.W.","year":"1977","unstructured":"Chen LB, Gudor RC, Sun T-T, Chen AB, Mosesson MW. Control of a cell surface major glycoprotein by epidermal growth factor. Science 1977; 197: 776-8.","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/jcp.1040890211","article-title":"Enhanced synthesis and extracellular accumulation of hyaluronic acid during stimulation of quiescent human fibroblast by mouth epidermal growth factor","volume":"89","author":"Lembach, K.J.","year":"1976","unstructured":"Lembach KJ. Enhanced synthesis and extracellular accumulation of hyaluronic acid during stimulation of quiescent human fibroblast by mouth epidermal growth factor. J Cell Physiol 1976; 89: 277-88.","journal-title":"J Cell Physiol"},{"key":"ref_27","first-page":"927","article-title":"Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor","volume-title":"Gut","volume":"22","author":"Konturek, S.J.; Brzozowski, T.; Piastucki, I.","year":"1981","unstructured":"Konturek SJ, Brzozowski T, Piastucki I, et al. Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor. Gut 1981; 22: 927-32."},{"key":"ref_28","first-page":"1134","article-title":"Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine","volume-title":"of adult rats. Gastroenterology 1986; 91","author":"Ulshen, M.H.; Lyn-Cook, L.E.; Raasch, R.H.","unstructured":"Ulshen MH, Lyn-Cook LE, Raasch RH. Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology 1986; 91: 1134-40."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000199280","article-title":"Effect of cell proliferation on healing of gastric and duodenal ulcers in rats","volume":"33","author":"Takeuchi, K.; Johnson, L.R.","year":"1986","unstructured":"Takeuchi K, Johnson LR. Effect of cell proliferation on healing of gastric and duodenal ulcers in rats. Digestion 1986; 33: 92-101.","journal-title":"Digestion"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.29.7.894","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T20:03:34Z","timestamp":1765656214000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.29.7.894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,7]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[1988,7,1]]},"published-print":{"date-parts":[[1988,7]]}},"alternative-id":["10.1136\/gut.29.7.894"],"URL":"https:\/\/doi.org\/10.1136\/gut.29.7.894","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1988,7]]}}}