Paracetamol given orally or subcutaneously did not produce any observable gastric mucosal damage, nor did it change the acidity of the residual secretion in rat stomachs. However, it delayed the gastric emptying rate and increased the residual volume of gastric secretion. Pretreatment with paracetamol 250 mg kg-1 significantly prevented ethanol-induced gastric ulceration. Although it did not influence ethanol-stimulated acid secretion, it increased the mucosal mucus content in the ethanol-treated animals. The findings suggest that the protective mechanism of paracetamol against ethanol-induced damage is likely to be due to improved gastric mucosal integrity, through an increase in the adherent mucosal mucus which protects the underlying delicate cellular structures.

The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage have been examined. The antiulcer action of subcutaneously (s.c.)-injected paracetamol, 250 mg kg-1, was attenuated by either subdiaphragmatic vagotomy or s.c. injection of N-ethylmaleimide, 10 mg kg-1. This attenuation was not seen in rats given paracetamol by the oral route (p.o.). Indomethacin pretreatment, 5 mg kg-1, did not influence the lesion-preventing action of paracetamol given s.c. or p.o. The findings suggest that the antiulcer effect of s.c.-administered paracetamol results from an action involving the vagal nerve and tissue sulfhydryls, but not prostaglandins. On the other hand, the protective mechanism of paracetamol p.o. is independent of the vagal system or tissue sulfhydryls and prostaglandins. It seems that paracetamol given p.o. exerts its antiulcer effect by acting directly on the mucosal cell to strengthen mucosal integrity.

The present study examines the protective effect of zinc sulphate against ethanol-induced gastric mucosal ulcers in rats. Absolute ethanol decreased the gastric mucosal blood flow and produced haemorrhagic lesions in the glandular mucosa. Zinc sulphate preincubation in an ex-vivo stomach chamber preparation prevented the formation of ethanol-induced lesions and attenuated the decrease of blood flow produced by ethanol. Subcutaneous injection of the same doses of the drug at 15 and 30 min before ethanol exposure, markedly reduced the blood flow and also aggravated ethanol-induced gastric injury; however, when injected at 23 and 24 h before ethanol administration, zinc sulphate protected against lesion formation but had no effect on the vascular changes induced by ethanol in the gastric glandular mucosa. These findings show that the antiulcer effect of zinc sulphate occurs only when the drug is given orally, or injected s.c. 23 and 24 h before ethanol challenge. Furthermore, this protective action is probably not entirely mediated by preservation of the gastric mucosal blood flow.

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