Paolo Carminati

The non‐steroidal anti‐inflammatory agent parsalmide prevents aspirin‐induced H+ back diffusion from the gastric lumen of the rat

parsalmide is a non steroidal anti-inflammatory agent (NSAIA) the pharmacological activity of which has been demonstrated (Capretti & Marinoni 1974; Ferrero et al 1976; Maffi et al 1976; Di Penta & Mastrangelo 1978). A special characteristic is its gastric tolerance (Carminati et al 1978, 1981). In the rat, it did not induce gastric erosions at doses much greater than those that inhibit oedema formation (Carminati et a1 1978). Paradoxically, i t has also been found to prevent the ulcerogenic effects of aspirin and other NSAIAs in the rat without interfering with their antiinflammatory activities (Carminati et al 1978). Our aim has been to see if parsalmide is able to counteract the disruption of the gastric mucosal barrier induced in the rat by aspirin. Aspirin is believed to induce local gastric damage by promoting back diffusion of H + ions present in the gastric lumen into the gastric mucosa (Davenport 1967). Female Sprague Dawley rats, 180 f 5 g, fasted for 24 h, were used. Abdomens were opened under light ether anaesthesia, then stomachs exposed and the gastric lumena gently washed with 4 ml of warm 0.9% NaCl (saline). Each pylorus was then tied with a silk thread and 4 ml of an aqueous solution of 100 mM HCI was immediately introduced into the lumen. A second ligature was then made around the cardiac end of the oesophagus. Dual ligation was used to minimize spontaneous gastric secretion (Levine 1%5) thus emphasizing the disappearance of H + ions from the gastric lumen. After the operation, which took about 3 min, the animals were returned to their cages and after 1 h were killed and the gastric juices collected for determination of volume and of residual H + (titration to pH 7 with 0.1 M NaOH) and Na+ (titration with a Beckman Astra 8 potentiometer with a Na-selective electrode) ions. Net flux of ions through the gastric mucosa was calculated by subtracting the amount of ion present at 0 time (rats killed immediately after instillation of gastric solution) and from the amount recovered 1 h after pyloric ligature. For the evaluation of the intrinsic effects of drugs on the ion fluxes, aspirin or parsalmide was directly introduced into the gastric lumen. To study the effect of parsalmide on the change of flux induced by aspirin, parsalmide was given either intragastrically (added to the solution introduced into the gastric lumen) or orally in a volume of 1 ml of 0.5% aqueous carboxymethylcellulose suspension, 2 h before dual ligation. Controls received the vehicle only. Parsalmide placed into the gastric lumen did not interfere to any significant extent with the titration of gastric solutions.