Association of chlorphentermine with phospholipids in rat alveolar lavage materials, alveolar macrophages and type II cells.
Ma-JY; Ma-JK; Weber-KC; Bowman-L; Reasor-MJ; Miles-PR
Appalachian Laboratory for Occupational Safety and Health, Morgantown, West Virginia :81-101
The effects of chlorphentermine (461789) on rat pulmonary surfactant phospholipids, alveolar macrophages, and type II cells were investigated in male Sprague-Dawley-rats. The rats were given three daily intraperitoneal injections of carbon-14 labelled or nonlabelled drug at a dose of 25mg/kg and were sacrificed on day four and lavage materials analyzed. In-vitro chlorphentermine binding to surfactant phospholipids was assayed in preparations from control animals by fluorometry with 1-anilino-8-naphthalene- sulfonate (ANS) as probe. Chlorphentermine enhanced ANS fluorescence in all phospholipid subfractions tested. Data for chlorphentermine binding to pulmonary lavage phospholipids indicated binding to different surfactant moieties with different affinities. Chlorphentermine was associated with the acellular surfactant phospholipids in the drug treated animals, and the cellular distribution in moles of chlorphentermine per mole of phospholipid was 0.056 for alveolar macrophages, 0.030 for type-II cells, and phospholipid fraction of the macrophages but appeared in free form in the alveolar type-II cells. The authors conclude that chlorphentermine is associated with phospholipid fractions from lung components and suggest a mechanism for chlorphentermine induced phospholipidosis based on an accumulation of surfactant phospholipids caused by a decreased rate of degradation in the presence of the drug.
Drugs; Laboratory-animals; In-vitro-studies; In-vivo-studies; Chlorinated-hydrocarbons; Chemical-binding; Lung-cells; Lipids; Cell-function; Physiology; Toxic-effects; Pulmonary-function; NIOSH-Publication
Appalachian Laboratory for Occupational Safety and Health, Morgantown, West Virginia