Gastroprotective effect of ranitidine bismuth citrate is associated with increased mucus bismuth concentration in rats.

摘要

BACKGROUND: Antisecretory and bismuth compounds protect the gastric mucosa from injury resulting from non-steroidal anti-inflammatory drugs. AIM: To study the mechanism underlying the gastroprotective effects of ranitidine bismuth citrate (GG311) in rats. METHODS: Indomethacin rat injury model and in vivo microscopy in which acid output, surface cell intracellular pH (pHi), gastric mucus gel thickness, and mucosal blood flow were measured simultaneously. RESULTS: In injury studies, GG311 dose dependently protected against severe injury induced by indomethacin (60 mg/kg subcutaneously). In in vivo microscopic studies, indomethacin significantly decreased mucus gel thickness and increased the initial rate of acidification of gastric surface cells when the superfusate pH was lowered from 7.4 to 1.0, and impaired pHi during acid exposure. Indomethacin had no effect on mucosal blood flow or acid output. GG311 alone had no effect on gel thickness, blood flow, or pHi homeostasis during acid exposure, but improved the initial acidification rate and pHi during superfusion with pH 1.0 solutions in the presence of indomethacin. In separate experiments, indomethacin pretreatment considerably increased gastric mucus bismuth concentrations in rats given GG311. CONCLUSIONS: The gastroprotective effect of GG311 against indomethacin induced gastric injury is associated with high and prolonged gastric mucus bismuth concentrations, which may impair proton permeation across the mucus gel.