Effects of low-dose phenytoin administered to rats fetuses on developing choroid plexus: kariometric study

RESUMO

The aim of the present study was to determine, by kariometric parameters, the influence of phenytoin, as teratogen, on the epithelial layer of choroid plexus in rats fetuses, using single daily dose ( 75 mg Kg-1 bd.wt.), during gestation GD9 to GD11, and lowest total dose used orally (225 mg Kg-1), to the best of our knowledge. In some of experimental studies in animals, the anticonvulsant drug phenytoin were administered in embriotoxic daily doses (100-1500 mg Kg-1 bd.wt.) increasing concentrations up to 20 times the human therapeutic plasma concentration. There is a significant lack of information regarding the embriotoxicity in pregnancy of these drug, phenytoin, in low doses. Phenytoin was administered in a single daily dose (75 mg Kg-1 bd.wt.) to pregnanty rats in GD9 to GD11 days of gestation, during organogenesis. Histological sections were obtained for analysis of nuclear alterations in the cuboidal epithelium of choroid plexuses of lateral ventricles in the rat fetuses. Eleven kariometric parameters were measured in each of the nuclei. Statistical comparison were made with Mann-Whitney's test. The nuclei of the phenytoin group showed significant reduction of the size parameters longest axis, mean axis, nuclear volume, nuclear area, nuclear perimeter, ratio of the longest axis to the shortest axis, ratio of the nuclear volume to the nucleararea) but not in shortest axis and shape parameters (contour index, shape factor and eccentricity) . A distinctive pattern of nuclear abnormalities in choroid plexus ephitelium of rat fetuses is associated with the use of low dose of phenytoin during pregnancy. Variations in nuclear size might reflect fundamental nuclear alterations of significance during the process of embriogenesis and could represent teratogenic influence of phenytoin in rats. Even at low dosage and short period of use during gestation, phenytoin can induce embriotoxicity.