Maternal and Fetotoxicity of Prenatal Propranolol Treatment: Range-finding Study of Dose Levels and Schedule of Administration

摘要

In order to assess the maternal and fetal toxicity and possible resultant subcellular alterations of cardiac development in the neonata, propranolol was administered by subcutaneous injection to pregnant rats on gestation days (GD) 8-10 or 8-20, at doses of 0, 25, 50, and 100 mg/kg/day. As a result of the longer dosing regime, maternal weight gain and pup weight on postnatal day (PND) 1 were significantly reduced at the two highest doses, and pup weight gain to PND 21 was significantly reduced at the highest dose; average litter size was unaffected. At PND 1, pup heart weight, protein, and DNA were significantly reduced at 100 mg/kg/day (only propranolol dose tested). At PND 21 (all doses tested), pup heart weight and protein were significantly reduced at 100 mg/kg/day; DNA and ornithine decarboxylase (ODC) were unaltered at 100 mg/kg/day, but ODC was significantly increased at 25 and 50 mg/kg/day. Beta-adrenergic receptor concentration was unaffected at all doses at both ages. In summary, the results indicate that maternal propranolol exposure using the longer dosing regime causes alterations in cardiac development at doses which cause maternal and fetal toxicity, and may lead to specific biochemical alterations at lower doses.