Garcia Garcia J, Martin Rollan C, Refoyo Enrinquez M A, Holgado Madruga M, Mariño Hernandez E, Macias Nuñez J F, Gomez Alonso A
Facultad de Medicina, Universidad de Salamanca, Spain.
J Surg Res. 1990 Feb;48(2):144-6. doi: 10.1016/0022-4804(90)90206-h.
Allopurinol, a xanthine-oxidase (XO) inhibitor, has been used to improve the resistance to ischemia with disappointing results that have been attributed to administration regimen of the drug. Our aim was to investigate the effect of different administration schedules of allopurinol on the survival in rats undergoing intestinal ischemia testing the blockade of XO. Intestinal ischemia was achieved by 90 min of clamping the superior mesenteric artery (SMA) close to its origin from the aorta. Three groups of animals were evaluated: A-group: only the allopurinol solvent was given; B-group: the full dose of allopurinol (100 mg/k b.w.) was given iv and C-group: the 75% dose was administered orally 24 hr before and the remaining 25% was administered 30 min before. Survival was evaluated at 48 hr and the blockade of XO was assayed by High Efficacy Liquid Chromatography (HELC) in homogenate of intestinal wall. Survival was only improved in the C-group (P = 0.02). Levels of hypoxanthine were significantly increased both in B-group and C-group (P = 0.003) when compared with the A-group. Levels of uric acid in B-group (P = 0.0003) and C-group (P = 0.0009) were significantly decreased with respect to A-group. That means that an effective blockade of XO is achieved whichever the regimen of administration. Allopurinol and oxypurinol levels were significantly increased (P = 0.05 and P = 0.008) in C-group when compared with B-group. We conclude that the protective effect of allopurinol on survival in intestinal ischemia in rats is not related to the blockade of XO but rather to the allopurinol and oxypurinol levels in intestinal wall.
别嘌醇是一种黄嘌呤氧化酶（XO）抑制剂，曾被用于提高对缺血的耐受性，但结果令人失望，这被归因于该药物的给药方案。我们的目的是研究别嘌醇不同给药方案对接受肠道缺血试验的大鼠存活情况的影响，并测试XO的阻断作用。通过夹闭肠系膜上动脉（SMA）靠近其从主动脉起源处90分钟来实现肠道缺血。评估了三组动物：A组：仅给予别嘌醇溶剂；B组：静脉注射全剂量别嘌醇（100mg/kg体重）；C组：在24小时前口服75%剂量，其余25%在30分钟前给药。在48小时时评估存活情况，并通过高效液相色谱法（HELC）在肠壁匀浆中测定XO的阻断情况。仅C组的存活率得到提高（P = 0.02）。与A组相比，B组和C组的次黄嘌呤水平均显著升高（P = 0.003）。B组（P = 0.0003）和C组（P = 0.0009）的尿酸水平相对于A组显著降低。这意味着无论给药方案如何，都能实现对XO的有效阻断。与B组相比，C组的别嘌醇和氧嘌呤醇水平显著升高（P = 0.05和P = 0.008）。我们得出结论，别嘌醇对大鼠肠道缺血存活的保护作用与XO的阻断无关，而与肠壁中的别嘌醇和氧嘌呤醇水平有关。
