Vitamin E supplementation in phenytoin induced developmental toxicity in rats: postnatal study.
OBJECTIVE
The aim of this study was to test the effect of supranutritional dosage of the natural antioxidant vitamin E (VitE) on phenytoin (PHT) induced developmental toxicity and possible long-term effects in rat offspring.


METHODS
PHT (150 mg/kg) was administered by oral gavage daily from day 7 to 18 of gestation and VitE prior to PHT orally on the same days.


RESULTS
PHT administration alone resulted in decreased survival rate and lower body weight of pups on day 21 post partum (PP). Moreover, PHT slightly changed somatic growth and pups failed to present dynamic air righting on days 15-20 PP. VitE supplementation did not alleviate these changes but rather induced persisting body weight reduction on the days 21 PP and 100 PP. We observed also decreased brain wet weight in the PHT and VitE + PHT groups compared to controls.


CONCLUSIONS
We concluded that prenatal supplementation with 500 mg/kg of VitE did not ameliorate the developmental toxicity of PHT and failed to protect postnatal development of rat offspring. Further, in the group supplemented with VitE, the occurrence of persistent body weight gain depression up to adulthood indicates its possible interference with somatic growth regulation.
Mach
Mojmír
M
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. mojmir.mach@savba.sk
Dubovický
Michal
M
Navarová
Jana
J
Kovacovský
Pavel
P
Ujházy
Eduard
E
D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D005260:Female; D005311:Fetal Hypoxia / Q000139:chemically induced*; D005328:Fetal Viability / Q000187:drug effects*; D048788:Growth and Development / Q000187:drug effects*; D008297:Male; D010672:Phenytoin / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control; D020011:Protective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D020011:Protective Agents; D014810:Vitamin E; D010672:Phenytoin