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Respiratory and non‐respiratory lung function indices during the development and resolution of O , S , S ‐trimethyl phosphorodithioate‐induced lung damage in the rat. A chemical model of adult respiratory distress syndrome
Author(s) -
Nemery Benoít
Publication year - 1987
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550070608
Subject(s) - lung , chemistry , respiratory system , putrescine , respiratory distress , anesthesia , pharmacology , endocrinology , medicine , biochemistry , enzyme
Arterial blood gases and the pulmonary uptake of putrescine and 5‐hydroxytryptamine (5‐HT) were studied between 6 h and 18 days after the administration to rats of an oral LD 50 ‐dose of the pneumotoxin, O , S , S ‐trimethyl phophorodithioate (OSSMe), a potential impurity in several organophosphorus insecticides. Aortic blood was sampled under pentobarbitone anaesthesia for measurements of arterial pH, and partial pressures of oxygen ( Pa O 2 ) and carbon dioxide ( Pa CO 2 ). Pa O 2 was significantly decreased 4 days after OSSMe administration, i.e. at the time of maximum lethality and increases in wet lung weight. This was accompanied by a significant increase in Pa CO 2 and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear, Pa CO 2 was slightly increased 2, 6 and 12 days after dosing. The uptake of putrescine (1,4‐diaminobutane) and of 5‐HT was measured by incubating lung slices with several concentrations of [ 3 H]‐putrescine and [ 14 C]−5‐HT, so as to estimate the apparent kinetic parameters of uptake, V max and K m . The V max for putrescine‐uptake was significantly decreased 1,2,4,6 and 12 days after the administration of OSSMe. The V max for 5‐HT‐uptake was significantly increased 1 day and significantly decreased 4 days after OSSMe administration. The uptake of 5‐HT is an endothelial function, and the decrease in 5‐HT‐uptake at 4 days may reflect injury to the pulmonary vascular endothelium at this time. The uptake of putrescine probably reflects the function of the pulmonary (mainly alveolar) epithelium. Alveolar type I cells are the cellular targets for the toxic action of OSSMe, and their destruction is followed by type II cell proliferation. The early and prolonged decrease in putrescine‐uptake, therefore, suggests that this function is different in proliferating type II cells as opposed to quiescent type II cells.