The role of aspirin in gastric ulceration

Abstract

The gastric irritant effects of aspirin were studied in rats treated with a variety of physical and "disease" (inflammatory) stress conditions (which may mimic responses to some stress states encountered clinically) with the object of establishing whether these stress states increase the susceptibility of the gastric mucosa to the potentially ulcerogenic actions of aspirin. While exposure to physical (eg, cold) stress conditions markedly increased the sensitivity of the gastric mucosa to aspirin, exposure to various disease stressors (eg, adjuvant arthritis, acute pain, or paw inflammation) did not appreciably affect the mucosal sensitivity to this drug. Attempts were made to determine the mechanisms of the physical stress plus aspirin interaction by use of pharmacological agents. The results suggest a major involvement of the parasympathetic-vagal, sympathetic, and histamine-producing systems, but not the adrenocortical axis, in this model of gastric ulcerogenesis. No differences were observed in the mucosal uptake of [14C]aspirin, showing that accelerated uptake of the drug is not a factor in the development of gastric ulceration.

Use of Inverted Intestinal Sacs to Assess the Effect of Gastrointestinal Insult on Carcinogen Absorption

“…The injurious effect of aspirin on the gastrointestinal tract is one of the major problems associated with the use of this analgesic [Menguy, 1978;Rainsford, 1978], The dose administered to the rats in the present ex periment was high, of the order associated with the treatment of arthritic conditions. It is assumed that the enhanced dimethylnitrosamine penetration results from damage to the intestinal permeability barrier.…”

“…The in verted sac technique, originally developed by Wiseman [1961], has been adapted to the screening of potential drugs for permeability [Kaplan, 1972] and the de termination of the principle site of absorption [Booth, 1968], In this experiment, inverted intestinal sacs were used to investigate the site and absorption of a hydro phobic polycyclic aromatic hydrocarbon (benzo(a)-pyrene) and also a lipid-and water-soluble carcinogen (dimethylnitrosamine). To achieve this, inverted in testinal sacs were prepared from animals which had been pretreated in the manner reported to induce gastrointestinal lesions with either aspirin [Menguy, 1978;Rainsford, 1978], stress [Beattie, 1977], 5-fluorouracil [Gardner and Heading, 1979;Losowsky et al, 1974] or with compounds implicated by epi demiological studies with increased cancer incidence, including alcohol [Becker, 1978;Wynder, 1976] and inhaled anaesthetics [Tomlin, 1979]. The rate of absorption of the two carcinogens via the intestines prepared from treated rats was then compared with that of control animals.…”