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Journal of hepato-biliary-pancreatic sciences

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion.


PMID 20878424

Abstract

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.