© 1984 Oxford University Press
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Effect of Chlorphentermine Pretreatment on the Distribution of Chlorphentermine in Isolated Perfused Rat Lungs1
Department of Pharmacology and Toxicology, University of Missisippi Medical Center Jackson, Mississippi 39216
Effect of Chlorphentermine Pretreatment on the Distribution of Chlorphentermine in Isolated Perfused Rat Lungs. ANGEVINE, L. S., LOCKARD, V. G., AND MEHENDALE, H. M. (1984). Fundam. Appl. Toxicol. 4, 202–209. Previous studies have shown that a 7-day treatment of rats with chlorphentermine (CP) enhances total pulmonary phospholipids and significantly enhances the accumulation of CP in perfused lungs. This study was conducted to determine if the accumulation of CP was associated with a particular fraction of the lung, and if the enhanced uptake correlated with the increased phospholipids. Rats were treated daily for 7 days with 50 mg/kg CP dissolved in saline and pair-fed controls received the vehicle only. On Day 8, the rats were sacrificed, and the lungs were removed, ventilated, and perfused. [14C]Chlorphentermine (5 µmol) was added to the perfusate of control and CP-pretreated lungs. After perfusion, the lung was homogenized and subjected to standard fractionation procedures. Some lungs were examined by light and electron microscopy. After 60 min of perfusion, CP uptake by lungs obtained from CP-treated rats was enhanced in comparison to uptake by lungs from control rats. However, CP was distributed uniformly among subcellular fractions, and CP pretreatment did not alter this pattern. Pulmonary macrophages obtained from CP-treated animals contained 8 times more CP than controls. Increased CP uptake following pretreatment can be accounted for by increased CP in the macrophages of treated rats. Macrophages in the lung tissue and in the lavage fluid from rats treated with CP were more numerous and larger than in control lungs. This suggests that a close association may be found between accumulated CP and macrophage uptake.