Amelioration of XXXX -induced @entity601 in @entity19 fetuses by maternal @entity1501 supplementation during gestation.

@entity1 @entity1501 @entity4181 @entity27797 @entity19 @entity1092 @entity48290 @entity2052 @entity601 @entity302 @entity39633
@entity1 of @entity302 @entity1 treated with @entity1092 ( @entity2052 ) during pregnancy have a higher risk of developing spina bifida than those of the general population. @entity2052 induces @entity601 in experimental animal embryos. But the pathogenetic mechanism remains rather elusive. Antiepileptic drugs (AED) in general accentuate pregnancy-imposed fall in maternal @entity1501 levels. Periconceptional @entity1501 supplementation is reported to protect embryos from developing @entity601 ( @entity601 ). Conflicting results have been reported by experimental studies that attempted to alleviate @entity2052 -induced @entity601 by @entity1501 . Our objectives were to determine the critical developmental stages and an effective dose of @entity1501 for the prevention of @entity2052 -induced @entity601 in @entity19 fetuses. A single teratogenic dose of 400 mg/kg of @entity2052 was administered to TO @entity19 on gestation day (GD) 7 or 8. It was followed by (1) a single dose of 12 mg/kg of FA ( @entity4181 ) or (2) 3 doses of @entity27797 mg/kg each. In experiment (3), FA (4 mg/kg) was administered thrice daily starting on GD 5 and continued through GD 10. These animals received @entity2052 on @entity39633 or 8. @entity2052 and B12 concentrations were determined by radioimmunoassay. The single heavy dose of FA had no rescue effect on @entity601 . Three divided doses of FA on @entity39633 and continuous dosing of FA from GD 5 through GD 10 substantially reduced the @entity2052 -induced @entity601 in the fetuses. In the later experiments, the neural folds elevated faster than the non-supplemented group. @entity2052 considerably reduced maternal plasma @entity1501 and @entity48290 concentrations. The heavy dose of FA only moderately improved vitamin levels. Three divided doses of FA elevated the vitamin levels slightly better but it was the prolonged dosing of FA that was associated with sustained elevation of plasma levels higher than the control levels and acceleration of neural tube closure thus accounting for the pronounced protection against @entity2052 -induced @entity601 development. These data suggest that plasma levels of FA and B12 have to be kept substantially elevated and maintained high throughout organogenesis period to protect embryos against @entity2052 -induced @entity601 in this @entity19 model.
