Prophylactic effect of rebamipide against the irritative and healing impairment actions of alendronate in rat stomachs

Abstract.

We examined the effect of rebamipide, an antiulcer drug, on the mucosal irritative and the healing impairment action of alendronate in rat stomachs. Male SD rats were used to examine the effect of rebamipide in the following 3 experiments. 1) Alendronate applied topically to the chambered stomach under urethane anaesthesia produced a decrease in the transmucosal potential difference and an increase of gastric mucosal blood flow and luminal acid loss, resulting in slight damage to the mucosa. Pretreatment with rebamipide for 3 days had no effect on the changes induced by alendronate. 2) Oral administration of alendronate caused non-haemorrhagic lesions in the stomach within 4 hr. Rebamipide, given either as a single p. o. injection or repeatedly for 7 days, did not significantly affect the lesions induced by alendronate. 3) Alendronate, given p. o. once daily for 1 week, markedly delayed the healing of acetic acid-induced gastric ulcers with the suppression of basic fibroblast growth factor (bFGF) expression. Rebamipide, given twice daily for 7 days, significantly promoted the delayed ulcer healing caused by alendronate, with the concomitant recovery of bFGF expression. These results suggest that rebamipide does not affect the direct irritating action of alendronate in the gastric mucosa, but this agent antagonizes the healing impairment action of alendronate by counteracting the downregulation of bFGF expression in the ulcerated mucosa.