CYTOPROTECTIVE EFFECT OF BISMUTH SUBSALICYLATE IN INDOMETHACIN-TREATED RATS IS ASSOCIATED WITH ENHANCED MUCUS BISMUTH CONCENTRATION

Background: Bismuth compounds prevent gastric injury from the short-te rm administration of nonsteroidal antiinflammatory drugs. We studied t he mechanisms underlying the gastroprotective actions of bismuth subsa licylate against indomethacin-induced injury in rats. Methods: An in v ivo microscopic technique was used in which acid output, surface cell intracellular pH (pH(i)), gastric mucus gel thickness and mucosaol blo od flow were measured simultaneously. Concentrations of bismuth in muc us were measured by atomic absorption. Results: Indomethacin (60 mg/kg ) significantly thinned the mucus gel layer and augmented the decrease of pH(i) during luminal acid superfusion, consistent with a weakened gastric mucosal barrier to acid. Bismuth subsalicylate partially rever sed this effect of indomethacin on pH(i), consistent with gastroprotec tion. Neither a prostaglandin-inhibiting but non-injurious dose of ind omethacin (5 mg/kg), bismuth subsalicylate, or their combination affec ted mucus gel thickness or pH(i) homeostasis. In separate experiments, indomethacin (60 mg/kg) significantly increased gastric mucus bismuth concentration in rats given bismuth subsalicylate. Conclusion: Bismut h accumulation in the gastric mucus during the evolution of mucosal in jury may play an important role in the gastroprotective effect of bism uth subsalicylate against indomethacin injury.