Department of Research, Kalamazoo Center for Medical Studies, Michigan State University, 1000 Oakland Drive, Kalamazoo, MI 49008, USA.
J Hepatobiliary Pancreat Sci. 2011 Mar;18(2):137-46. doi: 10.1007/s00534-010-0328-7.
Allopurinol was first introduced, in 1963, as a xanthine oxidase inhibitor when it was investigated for concomitant use with cancer chemotherapy drugs. Today it is used in gout and hyperuricemia. Due to its additive benefit in preventing oxidative damage, attention has shifted towards the use of allopurinol in organ ischemia and reperfusion.
Currently, the mechanism by which allopurinol exerts a protective benefit in ischemia reperfusion related events is not fully understood. There are various theories: it may act by inhibiting the irreversible breakdown of purine substrates, and/or by inhibiting the formation of reactive oxygen species, and/or by protecting against damage to the mitochondrial membrane.
This work focuses on liver ischemia and reperfusion injury in an effort to better understand the mechanisms associated with allopurinol and with this pathological entity.
The current research, mainly in animal models, points to allopurinol having a protective benefit, particularly if used pre-ischemically in liver ischemia reperfusion injury. Furthermore, after reviewing allopurinol dosing and administration, it was found that 50 mg/kg is statistically the most effective dose in attenuating liver ischemia reperfusion injury. Owing to the limited number of samples, the time of administration did not show statistical difference, but allopurinol was often beneficial when given around 1 h before ischemia.
In conclusion, allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the liver during ischemia and reperfusion.
别嘌醇于 1963 年首次被作为黄嘌呤氧化酶抑制剂被引入，当时它被用于联合癌症化疗药物。如今，它被用于治疗痛风和高尿酸血症。由于其在预防氧化损伤方面的附加益处，人们开始关注别嘌醇在器官缺血再灌注中的应用。
目前，别嘌醇在缺血再灌注相关事件中发挥保护作用的机制尚未完全阐明。有各种理论：它可能通过抑制嘌呤底物的不可逆转分解，和/或通过抑制活性氧的形成，和/或通过防止线粒体膜损伤来发挥作用。
这项工作专注于肝缺血再灌注损伤，旨在更好地理解与别嘌醇和这种病理实体相关的机制。
目前的研究主要集中在动物模型上，表明别嘌醇具有保护作用，特别是在肝缺血再灌注损伤中预先使用时。此外，在回顾了别嘌醇的剂量和给药后，发现 50mg/kg 是减轻肝缺血再灌注损伤的最有效剂量。由于样本数量有限，给药时间没有显示出统计学差异，但别嘌醇在缺血前 1 小时左右给药通常是有益的。
总之，别嘌醇通过其已知的黄嘌呤氧化酶抑制作用，作为潜在机制之一，已证明其在保护肝脏免受缺血再灌注损伤方面具有潜在的应用价值。
