Pulmonary toxicity of trichloroethylene: induction of changes in surfactant phospholipids and phospholipase A2 activity in the mouse lung.
Trichloroethylene (TCE) is a common organic solvent in use as a dry cleaning agent as well as an inhalant anesthetic. Nevertheless the effects of this material on the pulmonary surfactant which prevents alveolar collapse at maximal expiration is not known. Therefore, we have examined the effect of TCE on the intra- and extracellular surfactant pools and the activity of phospholipase A2, an enzyme which controls the remodeling of phosphatidylcholine to dipalmitoylphosphatidylcholine, the primary constituent of the pulmonary surfactant. Male CD-1 mice were treated ip with 2500 or 3000 mg/kg TCE. Twenty-four hours later mice were anesthetized and the lungs lavaged. Mice were then killed, the lungs perfused and excised, and subcellular fractions including lamellar bodies prepared. Some lungs were prepared for ultrastructural examination. Phospholipase A2 was assayed in all subcellular fractions. Phospholipid was assayed in the lavage (extracellular surfactant) and the lamellar bodies (intracellular surfactant). TCE (2500 mg/kg) caused selective exfoliation of Clara cells. However, only the dose of 3000 mg/kg TCE produced a significant decrease in the intracellular surfactant phospholipid. Minimal changes occurred in the phospholipid profiles. Phospholipase A2 specific activity was significantly decreased at both dosages within the lung microsomal fraction. In addition after treatment with 3000 mg/kg TCE the enzyme activity in the lamellar body fraction was significantly increased. These data suggest that inhalation of TCE may damage the enzymes which are responsible for synthesizing the pulmonary surfactant resulting in lower amounts of surfactant being stored and available for secretion into the alveolus.
Scott
J E
JE
Department of Anatomy, Dalhousie University, Halifax, Nova Scotia, Canada.
Forkert
P G
PG
Oulton
M
M
Rasmusson
M G
MG
Temple
S
S
Fraser
M O
MO
Whitefield
S
S
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010740:Phospholipases / Q000032:analysis*; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D010743:Phospholipids / Q000032:analysis*; D011663:Pulmonary Surfactants / Q000032:analysis*; D014241:Trichloroethylene / Q000633:toxicity*
D010743:Phospholipids; D011663:Pulmonary Surfactants; D014241:Trichloroethylene; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2