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-term administration of nonsteroidal antiinflammatory drugs. We studied the mechanisms underlying the gastroprotective actions of bismuth subsalicylate against indomethacin-induced injury in rats. Methods: An in vivo microscopic technique was used in which acid output, surface cell intracellular pH (pH(i)), gastric mucus gel thickness and mucosaol blood flow were measured simultaneously. Concentrations of bismuth in mucus 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 reversed this effect of indomethacin on pH(i), consistent with gastroprotection. Neither a prostaglandin-inhibiting but non-injurious dose of indomethacin (5 mg/kg), bismuth subsalicylate, or their combination affected 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: Bismuth accumulation in the gastric mucus during the evolution of mucosal injury may play an important role in the gastroprotective effect of bismuth subsalicylate against indomethacin injury.