Transplacental effects of allopurinol on suppression of oxygen free radical production in chronically instrumented fetal lamb brains during intermittent umbilical cord occlusion

Abstract

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.

Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia

“…However, animal studies have proven that allopurinol and oxypurinol pass through the blood/brain barrier and cause therapeutic concentrations in brain perfusate and cerebrospinal fluid. 9 10 Also, further experimental research in several species shows brain protection when allopurinol is given upon reperfusion and reoxygenation. 4 In addition, we feel that the relatively late start of the treatment, three to four hours after reperfusion, may have played an important role here.…”

Antenatal Allopurinol Reduces Hippocampal Brain Damage After Acute Birth Asphyxia in Late Gestation Fetal Sheep

“…Only 5 other studies in the literature have reported on antenatally administered allopurinol, but none of them have described any effects on the histology of the brain. 18,19,22,23,43 In the present study, therapeutic ranges of allopurinol and its metabolite oxypurinol have shown to be attainable after antenatal maternal treatment with allopurinol, while no adverse side effects were observed. These findings are in line with previous studies in both animals and humans.…”

“…18,22,23,43 Masaoka et al were the first to investigate antenatally administered allopurinol during intermittent umbilical cord occlusion in fetal sheep and described a significantly reduced production of superoxide in the allopurinol-treated animals. 22 This indicates a direct effect of allopurinol in preventing the production of free radicals, in scavenging free radicals once formed, or both. These results were confirmed in the ovine fetuses used in the present study, in which we found reduced indices of oxidative stress in the cardiovascular system after maternal treatment with allopurinol.…”

“…16 Therefore, there has been accumulating interest in establishing whether the perinatal cerebral outcome may be improved if the window of treatment with allopurinol is advanced, for instance via maternal treatment to cover the actual period of fetal asphyxia and of I/R in complicated labor. Maternal treatment with allopurinol crosses the placenta, it suppresses O 2 .À production in the fetus 22 and yields therapeutic levels in the neonatal circulation, 23 justifying this route of administration for preventative therapy in obstetric practice.…”

Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour

“…Allopurinol is metabolised into the active metabolite oxypurinol, which blocks uric acid production. Its plasma concentrations are therefore used in the monitoring of gout patients 21 22…”