Zahavi I, Fisher S, Marcus H, Heckelman B, Kiro A, Dinari G
Division of Pediatric Gastroenterology and Nutrition, Children's Medical Center of Israel, Petah Tiqva.
J Pediatr Gastroenterol Nutr. 1995 Aug;21(2):154-7. doi: 10.1097/00005176-199508000-00006.
Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used and may cause small intestinal inflammation and damage. Reactive oxygen metabolites are involved in various gastrointestinal inflammatory processes, but there is little information about their role in small intestinal mucosal damage induced by NSAIDs. We studied the effect of the oxygen radical scavengers superoxide dismutase (SOD), catalase (CAT), and allopurinol (ALLO) on indomethacin (INDO)-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg of INDO 30 min after refeeding 24 h-fasted rats. Total ulcer area was measured 24 h after INDO administration. Study groups each consisted of eight animals which received either i.p. CAT, SOD, or both together, at a dosage of 5,000 U/kg each. All drugs were divided into five doses, given once an hour over a 4-h period, starting at the time of INDO injection. Another group received 100 mg/kg ALLO in two doses. Total ulcer area was reduced by SOD from 228 +/- 12 (sq mm, mean +/- SEM) to 153 +/- 12 (p < 0.001), by CAT to 179 +/- 13 (p < 0.01), and by both together to 95 +/- 5 (p < 0.0001). ALLO administration reduced the total ulcer area to 176 +/- 7 (p < 0.003). The protective effect of oxyradical scavengers supports the hypothesis that oxygen radicals are involved in the pathogenesis of INDO-induced small intestinal ulceration in the rat.
非甾体抗炎药（NSAIDs）被广泛使用，且可能导致小肠炎症和损伤。活性氧代谢产物参与各种胃肠道炎症过程，但关于它们在NSAIDs诱导的小肠黏膜损伤中的作用，相关信息较少。我们研究了氧自由基清除剂超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和别嘌呤醇（ALLO）对吲哚美辛（INDO）诱导的大鼠肠道溃疡的影响。在禁食24小时的大鼠重新喂食30分钟后，通过皮下注射30mg/kg的INDO来诱发溃疡。在给予INDO 24小时后测量总溃疡面积。研究组每组由8只动物组成，分别腹腔注射CAT、SOD或两者，剂量均为5000U/kg。所有药物分为五个剂量，在INDO注射时开始，在4小时内每小时给药一次。另一组分两次给予100mg/kg的ALLO。SOD使总溃疡面积从228±12（平方毫米，平均值±标准误）减少到153±12（p<0.001），CAT使其减少到179±13（p<0.01），两者联合使用使其减少到95±5（p<0.0001）。给予ALLO使总溃疡面积减少到176±7（p<0.003）。氧自由基清除剂的保护作用支持了氧自由基参与INDO诱导的大鼠小肠溃疡发病机制的假说。
