Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats

Objective To study the effect of the nitric oxide donor, molsidomine, on ga stric and duodenal injury induced by indomethacin and aspirin. Methods Sprague-Dawley rats weighing 180-200 g were used after 24 h fasting . Indomethacin (5 mg/kg) was given subcutaneously as a single dose and foll owed by multiple injections of histamine. Molsidomine (0.05 mg/kg) or disti lled water was given by gavage 30 min before indomethacin and repeated at 3 h intervals for two doses. Rats were killed 2 h after the last dose of mol sidomine, Aspirin (500 mg/kg) was given by gavage and repeated 2.5 h later. Molsidomine or distilled water was given 30 min before the initial aspirin dose and repeated after 2 h. Animals were killed 2.5 h after the second do se of aspirin. The severity of the gastric mucosal damage was graded from 0 to 3, and the duodenal bulb ulcer surface area calculated by two independe nt observers using a dissecting microscope. Results Indomethacin and aspirin resulted in significant gastric mucosal da mage with median scores of 2 (interquartile ranges 1.4-3, n = 16 and 2-3, n = 10, respectively). Molsidomine significantly ameliorated indomethacin- a nd aspirin-induced damage with median scores of 1 (interquartile ranges 0.5 -1.5, n = 19 and 0.6-1.9, n = 10, respectively; P < 0.008 and P < 0.02, res pectively (Mann-Whitney Utest)), Molsidomine had no effect on duodenal bulb ulcerations caused by indomethacin. Conclusion Oral molsidomine has a protective effect on gastric mucosa again st damage induced by ulcerogenic agents. This could have an important clini cal benefit, especially in cardiac patients taking aspirin in addition to a nitric oxide donor such as molsidomine. (C) 2000 Lippincott Williams & Wil kins.