PHARMACOLOGY LETTERSTHE ROLE OF ENDOGENOUS ACID IN THE DEVELOPMENT OF ACUTE GASTRIC ULCER INDUCED BY ISCHEMIA-REPERFUSION IN THE RAT
Introduction
Many reports have discussed about acute gastric erosions induced by ischemia-reperfusion 1, 2, 3, 4, 5. They have suggested that the major pathogenesis of the erosions involved reactive oxygen species, microvascular dysfunction, leukocyte activation and the exhibition of luminal acid. Namely, ischemia seems to weaken mucosal integrity and make the mucosa exposed to the acid back diffusion 6, 7, 8, 9. Then, after reperfusion, the generation of reactive oxygen species from xanthine-xanthine oxidase system and activated leukocytes leads to tissue lipid peroxidation, mucosal microcircular dysfunction and finally death of mucosal cells together with the effects of luminal acid 1, 2, 4, 10. Recently, we have reported a new gastric ulcer model induced by ischemia-reperfusion of the celiac artery in the rat [11]. In this model, acute gastric erosions induced by ischemia-reperfusion have progressed to ulcers 48–72 hours after reperfusion. In this report, in order to clarify the mechanism in development of gastric erosions to ulcers, we investigated whether endogenous gastric acid may play an important role in the progression of the gastric damage. Therefore, we designed to measure the time-course changes of gastric acid secretion and the effects of anti-acid-secretory drugs that were administered at the various stages of gastric mucosal damages induced by ischemia-reperfusion in the rat.
Section snippets
Reagents
Cimetidine was obtained from Wako Pure Chemical Industries (Tokyo, Japan). Omeprazole was a gift from Fujisawa-Astra Pharmaceuticals (Osaka, Japan). All other chemicals were of reagent grade.
Ischemia-reperfusion induced gastric ulcer
All animal experiments were performed in accordance with the guidelines for animal experimentation in the Faculty of Medicine, Tottori University. Male Wistar rats weighing 250–300 g (SLC, Shizuoka, Japan) were fasted for 18 hours prior to the experiments but allowed free access to water. The
Gastric damage induced by ischemia-reperfusion
The time-course of gastric injury induced by ischemia-reperfusion are shown in Fig. 1. One hour after reperfusion, apparent erosive lesions were observed in the corpus. The total damaged area increased up to 12 hours after reperfusion. In the histological observations, these lesions progressed gradually towards the deep mucosa and finally, 48–72 hours after reperfusion, ulcers involving damage to the musclaris mucosae were observed. Fig. 2 shows the light-microscopic view of the gastric tissue
Discussion
Previously, it was reported that the treatment of rat celiac artery with ischemia (30min) and reperfusion (1 hour) causes acute gastric erosions 1, 4. In this erosion model, preadministration of anti-acid-secretory drugs, such as cimetidine and omeprazole, reduced the total area of erosions with the decrease in the secretion of endogenous acid [14], suggesting that luminal acid is necessary for the formation of erosive lesions by ischemia-reperfusion. In addition, we also developed the ulcer
References (18)
- et al.
Gastroenterology
(1986) - et al.
Eur. J. Pharmacol.
(1997) - et al.
Eur. J. Pharmacol.
(1995) - et al.
Gastroenterology
(1986) - et al.
Gastroenterology
(1987) - et al.
Life Sci.
(1996) - et al.
Free Radic. Res. Commun.
(1989) - et al.
Pharmacology
(1997) - et al.
Surgery
(1978)