EFFECT OF ALLOPURINOL ON URIC-ACID LEVELS AND BRAIN-CELL MEMBRANE NA-ATPASE ACTIVITY DURING HYPOXIA IN NEWBORN PIGLETS(,K+)

Oxygen-free radicals generated by xanthine oxidase during hypoxia-isch emia may result in cellular injury through harmful effects on membrane phospholipids. The present study investgated the effect of administra tion of allopurinol, an inhibitor of xanthine oxidase, on free-radical generation and brain cell membrane injury during hypoxia by inhibitin g the breakdown of hypoxanthine to uric acid. Brain cell membrane Na+, K+-ATPase activity and lipid peroxidation products (conjugated dienes and fluorescent compounds) were determined as indices of brain membran e function and structure. Cerebral oxygenation was continuously monito red during hypoxia by P-31-NMR spectroscopy. Plasma and brain tissue l evels of uric acid were measured to evaluate xanthine oxidase activity and purine degradation. Na+,K+-ATPase activity decreased significantl y in both hypoxic groups; however, the allopurinol-treated hypoxic gro up showed a smaller decrease than the untreated hypoxic group (47.3 +/ - 4.9 vs. 42.0 +/- 2.7 mu mol P-i/mg protein/h, P < 0.05), respectivel y. Conjugated dienes increased significantly in the untreated hypoxic compared to control animals (0.070 +/- 0.045 vs. 0.004 +/- 0.006 mu mo l/g brain, P < 0.05), with the allopurinol-treated animals having inte rmediate values (0.053 +/- 0.039 mu mol/g brain). Fluorescent compound s were lower in the allopurinol-treated hypoxic group compared to the untreated hypoxic group (0.79 +/- 0.19 vs. 1.06 +/- 0.60 mu g/quinine sulfate/g brain, P < 0.05). Measurements of serum and brain tissue uri c acid were significantly lower during hypoxia in the allopurinol-trea ted compared to the untreated group (30.3 +/- 15.6 vs. 45.7 +/- 10.6 m u M (P < 0.05) and 1.69 +/- 0.97 vs. 4.27 +/- 2.37 nmol/g (P < 0.05), respectively). Allopurinol is an effective inhibitor of xanthine oxida se and reduces the formation of uric acid in brain tissue under hypoxi c conditions. In addition, the present data suggest that allopurinol r educes lipid peroxidation during cerebral hypoxia in newborn piglets. Allopurinol, while unable to offer complete protection from the effect s of hypoxia, can attenuate hypoxic brain cell membrane injury.