Comparative pulmonary surfactant-inducing effect of three corticosteroids in the near-term rat

Abstract

Equivalent doses of dexamethasone, prednisolone, and betamethasone were given intraperitoneally to pregnant rats on day 20. Six dosage levels were selected: 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg/kg. Corticosteroids were diluted in saline solution containing 300 μCi of 3hcholine. Twenty-four rats (18 experimental, six control) were killed on day 21, four viable fetuses were removed from each, and the four pairs of fetal lungs from each rat were pooled. Phospholipids were extracted and separated by thin-layer chromatography. Incorporation of 3hcholine represented amounts of newly induced pulmonary lecithin and sphingomyelin. Results were expressed in terms of percentage change from control. Betamethasone appeared to be the most potent, with a statistically significant greater effect at the 6.4 mg/kg dosage level (two-factor analysis of variance, p = 0.03). There appeared to be a suppressive effect of all corticosteroids at the 12.8 mg/kg dosage level. If similar responses were observed in primates, the results would suggest that higher dosage levels of betamethasone (up to four times the presently recommended dose of ∼ 0.34 mg/kg) might be more efficacious.