ABSTRACT-Toclarify the mode of action of aminosalicylates, which are generally used as therapeutic agents for ulcerative colitis, we investigated the effect of some of the aminosalicylates on lipid peroxidation in the large intestinal mucosa after mesenteric ischemia/reperfusion in the rat. Although the cause of ulcerative colitis is unclear, Wilson (1) and Granger et al. (2) reported that it is partly due to oxygen-derived free radicals and the inflammation and tissue injury in this disease and that salicylazosulpha pyridine (SASP) and its metabolite [5-aminosalicylic acid (5-ASA)] might scavenge the oxygen-derived free radicals in gastrointestinal and small intestinal ischemia/reperfusion models. SASP is effective in the treatment and prophylaxis of ulcerative colitis. Although ulcerative colitis is generated in the large intestine, no study using large intestinal ischemia/reperfusion models has been reported. Therefore, we investigated the effect of aminosalicylates on mucosal lipid peroxidation after ischemia/reperfusion in the rat large intestine. We used 77 male Sprague-Dawley rats weighing 205-410 g (7 to 9-weeks-old; Charles River, Yokohama) in this study. After an overnight fast, the rats were anesthetized with urethane (50 mg/kg, i.p.). The body temperature was maintained at 37C by a heating pad. The rats underwent laparotomy, and the large intestinal lumen was flushed with 25 30 ml of warm sodium-phos phate-buffered saline (pH 7.4, bubbled with argon gas). The superior mesenteric artery and the inferior mesenteric artery were ligated according to the method of Megison et al. (3). Collateral arcades from the right coeliac artery and the jejunal arteries proximal to the site of occlusion were ligated to avoid the variable contribution of col lateral circulation to the distal ileum. To produce ische mia, atraumatic vascular clamps were then placed across the superior mesenteric artery and inferior mesenteric artery, and the bowel was then placed across the superior mesenteric artery and inferior mesenteric artery and returned to the abdominal cavity (10 min). After 10-min ischemia, for reperfusion, the clamps were removed from the superior mesenteric artery and inferior mesenteric artery (60 min). The rats in the sham-operated group underwent laparotomy, and the superior mesenteric artery, inferior mesenteric artery and collateral vessels were isolated but not occluded. In 6 rats in each group 3 ml of 5-[4-(2-carboxyethylcarbamoyl)-phenylazo]salicylic acid disodium salt dihydrate (BX661A), SASP, 5-ASA (0.01, 0.1, 1 mM), N-(4-aminobenzoyl)-ji-alanine (4-ABA, 1 mM) or sulphapyridine (SP, 1 mM) solution in phos phate-buffered saline was injected into the large intestinal lumen 1 min before reperfusion. Three milliliters of a mixture of superoxide dismutase (SOD, at 990 units/rat) and catalase (CAT, at 12,060 units/rat) was injected into large intestinal lumen 1 min before reperfusion (4). Five rats in the control group were given 3 ml of phosphate buffered saline 1 min before reperfusion. After 60 min repe...