The inhibitory action of sulphasalazine on ethanol‐induced gastric damage was studied in rats. Sulphasalazine (62.5 or 125 mg kg−1, s.c.) did not affect basal gastric acid secretion but increased pepsin output. Ethanol (40% v/v, 10 ml kg−1, p.o.) produced severe gastric glandular mucosal damage and lessened the stomach emptying rate of resin pellets, but it increased the levels of prostaglandin E2 (PGE2)‐like activity in the glandular mucosa. Sulphasalazine markedly prevented ethanol‐induced damage and significantly elevated gastric wall mucus levels both in basal conditions and in the presence of ethanol. Sulphasalazine caused a small insignificant increase in mucosal PGE2 levels in both control and ethanol‐treated rats. The drug significantly increased mucosal PGE2 levels in indomethacin‐treated animals, but did not prevent indomethacin‐induced mucosal damage. Sulphapyridine but not 5‐aminosalicylic acid, constituents of sulphasalazine, showed a similar antilesion action to the parent drug, and prevented gastric wall mucus depletion in ethanol‐treated animals. This study elucidates the protective effects of sulphasalazine against ethanol‐induced gastric lesions. The antagonistic action appears to be mediated, at least partly, through the preservation of gastric wall mucus by sulphapyridine.

The role of gastric glandular mucosal leukotriene C₄ in gastric ulceration, produced by restraint at 4 °C (stress) for 2 h in rats, was studied in relation to the ulcer-preventing effects of ethacrynic acid, sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), AA-861 and ONO-1078. Stress itself significantly raised mucosal leukotriene C4 levels; pretreatment with ethacrynic acid, sulphasalazine, sulphapyridine or AA-861 antagonised these changes and reduced the severity of gastric ulceration. Mucosal mast cell degranulation was prevented by ethacrynic acid, sulphasalazine, 5-aminosalicylic acid, AA-861 or ONO-1078; the mucus-depleting effect of stress was also reversed by all these drugs, except for 5-aminosalicylic acid. The anti-ulcer effect of ethacrynic acid and sulphasalazine appears to be related to their influence on glandular mucosal leukotriene C₄ levels.