Role of age in amphiphilic drug-induced pulmonary morphological and metabolic responses.

The morphological and metabolic responsiveness of pulmonary tissue to amphiphilic agents is dependent on age. Daily oral administration of chlorphentermine (60 mg/kg) for 1 wk produced an accumulation of phospholipid-rich hypertrophic macrophages in pulmonary alveoli accompanied by an increase in relative lung weight and elevation in levels of phosphatidylcholine (PC), sphingomyelin (S), phosphatidylserine (PS) plus phosphatidylinositol (PI), phosphatidylethanolamine (PE) plus phosphatidylglycerol (PG), and total phospholipid (TPL) in newborn rats. Chlorcyclizine treatment (60 mg . kg-1 . day-1) for 1 wk also resulted in an accumulation of hypertrophic macrophages and an increase in both TPL and PC levels in newborn lung. However, unlike chlorphentermine, the chlorcyclizine-stimulated increase in pulmonary cells was associated with no marked change in relative lung weight and levels of S, PG plus PE, and PS plus PI. Phenobarbital (30 mg/kg) reduced the chlorphentermine-induced (60 mg/kg) effect on neonatal relative lung weight, accumulation of hypertrophic macrophages, and phospholipid levels. Withdrawal from drug treatment for 2 wk in newborns previously given chlorphentermine for 7 days resulted in a disappearance of pulmonary hypertrophic macrophages and a return of TPL levels to control values. Our data support the view that age plays a role in the observed amphiphilic drug-induced morphological and metabolic responses in rat lung.