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)
Lampley
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EC
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Mishra
O P
OP
Graham
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Delivoria-Papadopoulos
M
M
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010672:Phenytoin / Q000627:therapeutic use*; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010672:Phenytoin; D000254:Sodium-Potassium-Exchanging ATPase