Transplacental effects of allopurinol on suppression of oxygen free radical production in chronically instrumented fetal lamb brains during intermittent umbilical cord occlusion.
OBJECTIVE
To evaluate the transplacental effect of allopurinol, which acts as a xanthine oxidase inhibitor and free radical scavenger, on inhibiting the production of superoxides during intermittent partial umbilical cord occlusion.


METHODS
Using four chronically instrumented fetal lambs, ewes received 400 mg allopurinol over a period of two hours. Concentrations of allopurinol and oxypurinol in blood samples from mothers and fetuses and fetal brain microdialysis perfusate were measured by HPLC. In another three cases the production of superoxide during intermittent umbilical cord occlusion was studied by measurement of chemiluminescence in perfusate before and after administration of Allopurinol.


RESULTS
(i) Allopurinol concentration in mothers had reached equilibrium by 30 min after starting administration and maintained a concentration about 6 mug/ml. Allopurinol concentration in fetuses increased gradually and reached 2.25 +/- 0.54 microg/ml at 120 min; (ii) Oxypurinol concentration in both mothers and fetuses increased during administration of allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates reached 0.32 +/- 0.12 microg/ml, 0.53 +/- 0.22 microg/ml at 120 min respectively; and (iv) Administration of allopurinol significantly suppressed superoxide production during intermittent partial umbilical cord occlusion.


CONCLUSIONS
These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.
Masaoka
Naoki
N
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Japan. masaoka@med.nihon-u.ac.jp
Nakajima
Yoshiyuki
Y
Hayakawa
Yasuhito
Y
Ohgame
Sachiko
S
Hamano
Satoshi
S
Nagaishi
Masaji
M
Yamamoto
Tatsuo
T
D000493:Allopurinol / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005311:Fetal Hypoxia / Q000097:blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D016166:Free Radical Scavengers / Q000097:blood / Q000493:pharmacokinetics*; D018384:Oxidative Stress / Q000187:drug effects*; D010117:Oxypurinol / Q000097:blood; D010920:Placenta; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012756:Sheep; D013481:Superoxides / Q000032:analysis; D014470:Umbilical Cord / Q000098:blood supply; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013481:Superoxides; D000493:Allopurinol; D014969:Xanthine Oxidase; D010117:Oxypurinol