Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid

Most of non-steroidal anti- inflammatory drugs (NSAIDs) except aspirin (ASA ) produce intestinal damage in rats. In the present study, we re-examined t he intestinal toxic effect of ASA in rats, in comparison with various NSAID s, and investigated why ASA does not cause damage in the small intestine, i n relation to its metabolite salicylic acid (SA). Various NSAIDs (indometha cin; 10 mg/kg; flurbiprofen; 20 mg/kg; naproxen; 40 mg/kg; dicrofenac; 40 m g/kg; ASA; 20-200 mg/kg) were administered s.c., and the small intestinal m ucosa was examined macroscopically 24 h later. All NSAIDs tested, except AS A, caused hemorrhagic lesions in the small intestine, with a decrease of mu cosal PGE(2) contents. ASA did not provoke any damage, despite inhibiting ( prostaglandin) PG production, and prevented the occurrence of intestinal le sions induced by indomethacin, in a dose-related manner. This protective ac tion of ASA was mimicked by the equimolar doses of SA (17.8-178 mg/kg). Ind omethacin caused intestinal hypermotility, in preceding to the ocurrence of lesion, and this event was followed by increases of enterobacterial transl ocation in the mucosa. Both ASA and SA prevented both the intestinal hyperm otility and the bacterial translocation seen after indomethacin treatment. In addition, the protective effect of SA was not significantly influenced b y either the adenosine deaminase or the adenosine receptor antagonists. Fol lowing administration of ASA, the blood SA levels reached a peak within 30 min and remained elevated for more than 7 h. These results suggest that SA has a cytoprotective action against indomethacin-induced small intestinal l esions, and this action may be associated with inhibition of the intestinal hypermotility and the bacterial translocation, but not mediated by endogen ous adenosine. Failure of ASA to induce intestinal damage may be explained, at least partly, by a protective action of SA, the metabolite of ASA. (C) 2001 Elsevier Science Ltd. All rights reserved.