Neuroprotective effect of phenytoin against in utero hypoxic brain injury in fetal guinea pigs.

The present study tests the hypothesis that phenytoin, an antiepileptic agent known to block Na+ and Ca2+ channels, will prevent hypoxic brain injury in the fetus by preventing lipid peroxidation and preserving Na+,K(+)-ATPase activity. Studies were performed in 37 fetuses obtained from pregnant guinea pigs at 58-60 days gestation (term). The pregnant guinea pigs were divided into four groups: a normoxic group, a hypoxic group, a normoxic group treated with phenytoin, and a phenytoin treated hypoxic group. There were eight to ten fetal guinea pigs in each group. The treatment groups were given phenytoin 30 mg/kg (50 mg phenytoin/ml solvent) intraperitoneally. Hypoxia was induced by exposing the guinea pigs to 7% oxygen for 60 min. This level of hypoxia has been shown to decrease ATP and phosphocreatine levels by 90%. The fetal brains were harvested and the brain cell membranes were prepared from each group of fetuses. Na+,K(+)-ATPase activity and lipid peroxidation products, measured as relative fluorescent intensity, were determined. The mean Na+,K(+)-ATPase activity in the control, hypoxic, phenytoin-normoxic and phenytoin-hypoxic groups was 56.4 +/- 9.7, 37.9 +/- 10.6, 47.0 +/- 8.4 and 52.0 +/- 9.7 mumol inorganic phosphate/mg protein per h, respectively. The hypoxic group had significantly less Na+,K(+)-ATPase activity than both the normoxic group (P < 0.01), and the phenytoin treated hypoxic group (P < 0.05). There was no significant difference between the normoxic group and either of the phenytoin-treated groups (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)