Effect of allopurinol on uric acid levels and brain cell membrane Na+,K(+)-ATPase activity during hypoxia in newborn piglets.
Oxygen-free radicals generated by xanthine oxidase during hypoxia-ischemia may result in cellular injury through harmful effects on membrane phospholipids. The present study investigated the effect of administration of allopurinol, an inhibitor of xanthine oxidase, on free-radical generation and brain cell membrane injury during hypoxia by inhibiting 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 membrane function and structure. Cerebral oxygenation was continuously monitored during hypoxia by 31P-NMR spectroscopy. Plasma and brain tissue levels of uric acid were measured to evaluate xanthine oxidase activity and purine degradation. Na+,K(+)-ATPase activity decreased significantly in both hypoxic groups; however, the allopurinol-treated hypoxic group showed a smaller decrease than the untreated hypoxic group (47.3 +/- 4.9 vs. 42.0 +/- 2.7 mumol Pi/mg protein/h, P < 0.05), respectively. Conjugated dienes increased significantly in the untreated hypoxic compared to control animals (0.070 +/- 0.045 vs. 0.004 +/- 0.006 mumol/g brain, P < 0.05), with the allopurinol-treated animals having intermediate values (0.053 +/- 0.039 mumol/g brain). Fluorescent compounds were lower in the allopurinol-treated hypoxic group compared to the untreated hypoxic group (0.79 +/- 0.19 vs. 1.06 +/- 0.60 micrograms/quinine sulfate/g brain, P < 0.05). Measurements of serum and brain tissue uric acid were significantly lower during hypoxia in the allopurinol-treated compared to the untreated group (30.3 +/- 15.6 vs. 45.7 +/- 10.6 microM (P < 0.05) and 1.69 +/- 0.97 vs. 4.27 +/- 2.37 nmol/g (P < 0.05), respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Marro
P J
PJ
Department of Pediatrics, Maine Medical Center, Portland 04102.
McGowan
J E
JE
Razdan
B
B
Mishra
O P
OP
Delivoria-Papadopoulos
M
M
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D010100:Oxygen / Q000037:antagonists & inhibitors*; D011687:Purines / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D014527:Uric Acid / Q000378:metabolism*
D005609:Free Radicals; D011687:Purines; D014527:Uric Acid; D000493:Allopurinol; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen