The morphology of gastric lesions induced by aspirin in the rat and their modification by pretreatment with zinc acexamate (100 mg/kg) were studied by scanning electron microscopy. The influence of mucosal levels of prostaglandin E2 (PGE2) on the development of these lesions was also investigated. High (200 mg/kg) or low (50 mg/kg) doses of aspirin inhibited PGE2 production similarly, but the morphology of these lesions differed considerably. While gross exfoliation of extensive areas of gastric mucosa was observed after 200 mg/kg aspirin, only ultrastructural lesions of surface epithelial cells were present after 50 mg/kg aspirin. Regardless of the dose of aspirin administered, pretreatment with zinc acexamate raised PGE2 levels and increased the presence of mucus. Our results showed that after zinc acexamate, the development of deep erosions appearing with high doses of aspirin was prevented and the ultrastructural lesions induced by low doses of aspirin were not observed. The fact that zinc acexamate did not modify the anti-inflammatory action of aspirin in the carrageenin-induced oedema model suggests that the protective effect of zinc acexamate is exerted locally on the gastric mucosa.
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