Pulmonary endothelial and alveolar epithelial lesions induced by O,O,S-trimethyl phosphorothioate in rats.
The morphogenesis of pulmonary injury induced by an impurity present in a commercially important organophosphorus insecticide, O,O,S-trimethyl phosphorothioate (OOS-TMP), was studied by combined light and transmission electron microscopy. Weanling female WAG/Rij rats received OOS-TMP dissolved in corn oil by gavage and were studied at intervals from 6 to 168 h after treatment. Sequestration of neutrophils was initially observed at 12 h after treatment and was accompanied by interstitial oedema. Plasmalemma alterations in endothelium lining capillaries and small arteries and veins were observed from 12 to 120 h after treatment and were accompanied by endothelial cell detachment and separation from the basal lamina. Abundant aggregates of fibrin were sequentially observed in intravascular, interstitial, and alveolar spaces. Platelet aggregation and degranulation were occasionally observed in capillaries as early as 12 h after treatment, and frequently observed in capillaries and small vessels from 24 to 96 h after treatment. Significant increases in wet lung weight and lung water content occurred at the same time that morphologic changes were observed in pulmonary endothelium. Alterations in type I alveolar epithelial cells were initially observed at 24 h after treatment. Cell swelling, fragmentation, and necrosis were observed in both type I and type II cells and resulted in a bare basal lamina. Marked attenuation, hypertrophy, and proliferation of type II epithelial cells followed alveolar epithelial cell injury and loss. Minimal changes were observed in non-ciliated bronchiolar epithelial (Clara) cells; predominant changes included the loss of surface microvilli and apical cytoplasmic bulge. The results of this study indicate that the endothelium and alveolar epithelium are the predominant cell types in the rat lung injured following OOS-TMP administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Durham
S K
SK
Division of Health Research, Netherlands Organization for Applied Scientific Research TNO, Rijswijk.
Mezza
L E
LE
Imamura
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008854:Microscopy, Electron; D009504:Neutrophils; D009929:Organ Size / Q000187:drug effects; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010974:Platelet Aggregation; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C019123:O,O,S-trimethyl phosphorothioate; D006909:Hydroxyproline