Influence of protein malnutrition on susceptibility to induction of cleft palate by cortisone in mice 1,2

ABSTRACT

The objective of the present work is to evaluate the possible influence of protein malnutrition on drug teratogenicity by utilizing the well established experimental model for cleft palate induction by cortisone in mice. The study was performed on 150 female pregnant albino Swiss mice. Animals were fed throughout pregnancy either by balanced normal diet [20% casein] or by low protein diet [5% casein]. Hydrocortisone acetate was administered intramuscularly in the dose levels of 2.5 and 5.0 mg daily from the 11th to the 14th day of gestation [vaginal plug marks day 1]. The outcome of pregnancy was examined at day 18th for implantations, resorptions, viability of fetuses, fetal body weights and external anomalies. The fetal palates were examined histologically. The obtained results showed that protein malnutrition increases the incidence of resorptions and decreases the fetal body weights. These effects were potentiated following cortisone treatment. The state of protein malnutrition did not induce cleft palates, but it increased the incidence of cleft palates from 77.5 to 97.0% and from 84.4 to 100% following the administration of 2.5 and 5.0 mg/kg of hydrocortisone, respectively. Thus, protein malnutrition potentiates the teratogenecity of cortisone in mice. The possible mechanisms for this action are discussed