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We produced ulcers in the antrum by administering BPPs to fasted rats, followed by refeeding, and confirmed their healing\u2010impairment action on pre\u2010existing gastric ulcers; the ulcerogenic effect is due to direct mucosal irritation and decrease in the mucosal anti\u2010oxidative system, while the latter effect is due to dysregulation of growth factor expression, such as vascular endothelial growth factor and basic fibroblast growth factor, and angiogenesis in the ulcerated mucosa. In this article, we describe these two animal models for investigating BPP\u2010related adverse reactions, including methods for the induction of antral ulcers and healing impairment of gastric ulcers, as well as measurement of pathogenic functional and biochemical changes.<jats:italic>Curr. Protoc. Toxicol<\/jats:italic>. 53:21.10.1\u201021.10.29. \u00a9 2012 by John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/0471140856.tx2110s53","type":"journal-article","created":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T13:36:05Z","timestamp":1345037765000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Gastric Ulcerogenic and Healing Impairment Effects of Bisphosphonates: Adverse Gastric Reactions of Bisphosphonate"],"prefix":"10.1002","volume":"53","author":[{"given":"Koji","family":"Takeuchi","sequence":"first","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"}]}],"member":"311","published-online":{"date-parts":[[2012,8]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-007-1592-2"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-9769-5"},{"key":"e_1_2_16_4_1","first-page":"609","article-title":"Gastric ulcerogenic and healing impairment effects of risedronate, a nitrogen\u2010containing bisphosphonate, in rats: Comparison with alendronate and minodronate","volume":"62","author":"Amagase K.","year":"2011","journal-title":"J. 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