Effect of allopurinol on brain adenosine levels during hypoxia in newborn piglets

Adenosine, a purine nucleoside, is a potent inhibitory neuromodulator in the brain which may provide an important endogenous neuroprotective role during hypoxia-ischemia. Allopurinol, a xanthine oxidase inhibitor, blocks purine degradation and may result in the accumulation of purine metabolites, including adenosine, during hypoxia. The present study determines the effect of allopurinol administration prior to hypoxia on brain levels of adenosine and purine metabolites in the newborn piglet. Twenty-two newborn piglets (age 3-7 days) were studied: 5 untreated normoxic and 6 allopurinol-treated normoxic controls were compared to 5 untreated hypoxic and 6 allopurinol-treated hypoxic animals. Brain tissue energy metabolism was continuously monitored during hypoxia by (31)P NMR spectroscopy. Brain tissue levels of purines increased in both hypoxic groups during hypoxia, however, there were significantly higher increases in brain tissue levels of adenosine (66.5 +/- 30.5 vs. 19.4 +/- 10.7 nmol/gm), P < 0.01 and inosine (265 +/- 97.6 vs. 162.8 +/- 38.3 nmol/gm), P = 0.05 in the allopurinol-treated hypoxic group. Allopurinol inhibits purine degradation under severe hypoxic conditions and results in a significant increase in brain tissue levels of adenosine and inosine. The increased accumulation of CNS adenosine during hypoxia which is seen in the allopurinol-treated animals may potentiate adenosine's intrinsic neuroprotective mechanisms.