title: Gastric ulcerogenic and healing impairment actions of alendronate, a nitrogen-containing bisphosphonate - prophylactic effects of rebamipide.
abstract: Alendronate, a nitrogen containing bisphosphonate (BPP), when given p.o., decreases the transmucosal potential difference by direct irritating action, resulting in non-hemorrhagic lesions in both the corpus and antrum of fasted rats, and after re-feeding produces large ulcers in the antrum with increased vascular permeability and submucosal edema. The pathogenesis of these ulcers may be explained by the impairment of the mucosal anti-oxidative system and does not involve acid digestion as well as a deficiency of prostaglandins (PGs). Alendronate, although does not affect cyclooxygenase/ PGE(2) production in the ulcerated mucosa, but impairs the healing of gastric ulcers in rats, and this effect may be related to the down-regulation of vascular endothelial growth factor and basic fibroblast growth factor (bFGF), the important growth factors for the vascularization/granulation as well as the suppression of the stimulatory action of epidermal growth factor on the epithelial proliferation/migration. Rebamipide, a mucosal protective and antiulcer drug, does not affect the direct irritating action of alendronate in the gastric mucosa but prevents the alendronate-induced antral ulceration, probably due to anti-oxidative and anti-inflammatory actions. In addition, this agent also antagonizes the healing impairment action of alendronate by counteracting the down-regulation of bFGF expression in the ulcerated mucosa. It is assumed that rebamipide is a promising drug that can be used as a prophylactic against the adverse effects of BPPs in the stomach.
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. takeuchi@mb.kyoto-phu.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kato
authors.forename: Kikuko
authors.initials: K
authors.lastname: Amagase
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019386:Alendronate / Q000009:adverse effects*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D006801:Humans; D015363:Quinolones / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000897:Anti-Ulcer Agents; D050071:Bone Density Conservation Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine; D019386:Alendronate