Drug-Induced Foam Cell Reactions in Rats, II. Chemical Analysis of Lipids Stored in Lungs and Foam Cells after Treatment with Chlorphentermine, 5-[p-(Fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (RMI 10.393) and 1-Chloramitriptyline

Abstract

Lipidosis and foam cell reaction was induced in rat lungs by repeated administration of chlorphentermine, RMI 10.393 (=5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol), and 1-chloramitriptyline. Foam cell and lung lipids were extracted and separated in classes by thin-layer chromatography. Phospholipids were determined by phosphorus analysis, while neutral lipids were measured densitometrically. In lungs of drug-treated rats lecithin, phosphatidyl glycerol, phosphatidic acid, phosphatidyl inositol and free fatty acids accumulated in varying amounts. All other lipids were present in normal or reduced concentrations. Foam cells of chlorphentermine- and RMI 10.393-treated rats contained mainly phospholipids, i.e. lecithin and only small amounts of neutral lipids, i.e. cholesterol. Foam cells induced by 1-chloramitriptyline contained besides phospholipids also large amounts of neutral lipids, i.e. cholesterol, free fatty acids and cholesterol esters. This study and recent reports of others show that certain drugs produce a generalized metabolic disturbance characterized by accumulation of various lipids in several tissues. The distribution patterns of lipids induced by various drugs may differ considerably. This indicates that several biochemical mechanisms may be involved in the pathogenesis of drug-induced lipidosis.