Drug-induced foam cell reactions in rats: I. Histopathologic and cytochemical observations after treatment with chlorphentermine, RMI 10.393 and Ro 4-4318

Abstract

Female rats were treated with graded oral doses of the anorectic chlorphentermine, RMI 10.393, an inhibitor of platelet aggregation, and of Ro 4-4318, a tricyclic amine belonging to a series of experimental psychotropic drugs, for 2–16 days. Masses of foam cells accumulated in the alveoli and bronchi of the lungs. With the higher doses foam cells were also demonstrated in the red pulpa of the spleen, in peribronchial lymphatic tissue, and in one animal also in the thymus. The extent of the foam cell reaction was related to dose and duration of treatment. A method for the isolation of alveolar foam cells was developed. Cytochemical studies on isolated foam cells showed that they contained large amounts of phospholipids, i.e., phosphoglycerides (lecithin), sphingomyelin and plasmalogens, and probably also small amounts of free fatty acids, cholesterol and acid mucopolysaccharides. No evidence was found for the presence of triglycerides, sulfatides, gangliosides, glycogen, iron and neutral mucopolysaccharides. These changes are a reflection of a drug-induced generalized disturbance of the phospholipid metabolism. The mechanism and toxicologic significance are not as yet explained.