Abstract
Nonsteroidal antiinflammatory drugs (NSAIDs) produce gastric damage in experimental animals, irrespective of the route of administration. However, aspirin (ASA) causes damage only when it is given orally. In the present study, we examined the gastric ulcerogenic effect of subcutaneously administered ASA in rats, in comparison with various NSAIDs, and investigated the reason why ASA does not cause damage in the stomach, in relation to its metabolite salicylic acid (SA). Since the antiinflammatory action of SA is known to be mediated, partly, by endogenous adenosine (AD), we also examined the possible involvement of AD in the protective action of SA. Various NSAIDs (indomethacin, flurbiprofen, naproxen, diclrofenac, ASA, SA) were administered subcutaneously, and the gastric mucosa was examined macroscopically 4 hr later. All NSAIDs tested, except ASA and SA, caused hemorrhagic lesions in the stomach, with a marked gastric hypermotility and a decrease of mucosal PGE2 contents. These ulcerogenic and motility responses caused by NSAIDs were blocked by pretreatment with atropine or PGE2. ASA, although inhibiting PGE2 generation, caused neither hypermotility nor damage in the stomach. On the other hand, SA alone inhibited basal gastric motility without any effect on mucosal PGE2 contents, and this agent, when given together with indomethacin, prevented gastric hypermotility and lesion formation in response to indomethacin, without affecting the reduced PGE2 contents. Likewise, ASA inhibited these responses to indomethacin, yet the effects appeared later than those of SA. Following administration of ASA, the blood SA levels reached a peak within 30 min and remained elevated for 4 hr. In addition, the protective effect of SA was not significantly influenced by either the AD deaminase or the AD-receptor antagonists. These results suggest that the failure of parenteral ASA to induce gastric damage may be explained by a protective action of SA metabolized from ASA. SA has a cytoprotective action against NSAID-induced gastric lesions, and this action is not mediated by endogenous AD but may be functionally associated with inhibition of the gastric motility response.
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