Chlorphentermine-induced neonatal and maternal pulmonary phospholipidosis in rats

Pregnant rats were treated on Days 16-20 of pregnancy with 30 mg/kg chlorphentermine hydrochloride (CP) or an equal volume of 0.9% NaCl. Females delivered on Day 21 and neonates were examined 12 hr postpartum. Electron micrographs showed the CP neonates to have lamellar inclusions, characteristic of drug-induced phospholipidosis in Type I and Type II cells, macrophages, and nonciliated bronchiolar epithelial cells of the lung. These inclusions were either unicentric, multicentric, or consisted of whorls of membranous material. The content of total phospholipids was increased in neonatal lung as a result of CP treatment. A decrease in the percentage of total phospholipid present as phosphatidylinositol plus phosphatidylserine and an increase in the content of disaturated phosphatidylcholine were found in neonatal lung as a result of maternal chlorphentermine treatment. In maternal lung, increases were seen in the content of total phospholipids, total phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylinositol plus phosphatidylserine. A decrease in the percentage of sphingomyelin was also found. The results of this study indicate that following prepartum maternal administration of CP morphological changes are accompanied by biochemical alterations which are consistent with the induction of phospholipidosis as observed in neonatal lung. These biochemical changes were different than those associated with the induction of this disorder in the maternal lung.