Alterations in newborn and adult rat lung morphology and phospholipid levels after chlorcyclizine or chlorphentermine treatment

Abstract

Daily, po administration of chlorcyclizine at doses of 10, 30, or 60 mg/kg for 7 days to adult or newborn rats did not significantly alter relative lung to body weight. Only in the case of newborns administered 60 mg/kg/day chlorcyclizine for 1 week was there an accumulation of hypertrophic macrophages in pulmonary alveoli accompanied by an increase in total phospholipid and phosphatidylcholine levels. In comparison, varying chlorcyclizine doses given po for 7 days failed to alter adult lung morphology and phospholipid levels. While prolongation of chlorcyclizine treatment (60 mg/kg/day) for 2 weeks failed to markedly change relative lung weight in adults and newborns, an equivalent chlorphentermine dose significantly elevated this weight in either group. In adults, chlorcyclizine treatment for 2 weeks produced an accumulation of alveolar hypertrophic macrophages; however, this reaction occurred after 1 week in newborns. The chlorcyclizine-induced foam cell development in either age group was associated with an increase in lung phosphatidylcholine and total phospholipid as well as a fall in glycogen levels. In newborns or adults administered chlorphentermine, the resultant accumulation of hypertrophic macrophages was accompanied by a rise in total phospholipid as well as a rise in all individual phospholipid classes extracted but without a marked change in glycogen content. In view of the differences in lung responsiveness between chlorphentermine and chlorcyclizine, our data suggest that time and dose play a role in the observed drug-induced pulmonary phospholipidosis.