Roles of intrinsic prostaglandins and leukotrienes in gastric mucosal damage

Abstract

While gastric mucosa contains prostaglandins and leukotrienes, the roles of these substances in the gastric mucosal protection and damage are not clarified. Using AA-861, a specific 5-lipoxynenase inhibitor, and indomethacin, a cyclooxygenase inhibitor, we investigated the roles of intrinsic prostaglandins and leukotrienes in the gastric circulatory change and the development of gasstric lesion induced by ethanol.
Rats were fasted for 48 hours and allowed free access to water. After light ether anesthesia, rats were orally given AA-861 (gift from Takeda Chem. Industry; 2.5, 10, 40 or 640mg/kg), indomethacin (20mg/kg), and the both or AA-861 (40mg/kg) and indomethacin (20mg/kg). Thirty min after the treatment, 2ml of ethanol (30, 40, 70, 99.5%) was orally administered. Sixty min later, the rats were killed to measure the area of mucosal lesions. The gastric mucosa was damaged by ethanol (≥40%) in a dose-dependent manner. The treatment with AA-861 prohibited the gastric mucosal damage. However, the treatment with indomethacin did not show a significant influence to the mucosal damage. Combined treatment of AA-861 and indomethacin yielded no significant difference from that of single treatment with AA-861 in acute gastric mucosal ulceration.
The mucosal blood flow velocity was monitored by laser doppler velocimetry before and after the ethanol administration in the groups treated with vehicle, AA-861 or indomethacin. The blood flow velocity decreased after the administration of 40% ethanol in the group treated with indomethacin, and in a group treated with vehicle. By contrast, in the group treated with AA-861, the velocity did not show a significant decrease after the ethanol administration.
The results suggested that the basal level of intrinsic prostaglandins may not affect the mucosal protection against the gastric injury induced by high concentration of ethanol, and that the formation of gastric mucosal lesion induced by ethanol may be due to the increase of leukotrienes in gastric musoca, which caused the decrease of gastric mucosal flow velocity resulting in the mucosal injury.