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.
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 LD50-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 (PaO2) and carbon dioxide (PaCO2). PaO2 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 PaCO2 and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear, PaCO2 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 [3H]-putrescine and [14C]-5-HT, so as to estimate the apparent kinetic parameters of uptake, Vmax and Km. The Vmax for putrescine-uptake was significantly decreased 1, 2, 4, 6 and 12 days after the administration of OSSMe. The Vmax 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Medical Research Council, Toxicology Unit, Carshalton, Surrey, U.K.
B
B
Nemery
D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012129:Respiratory Function Tests; D012701:Serotonin / Q000378:metabolism
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C033125:O,S,S-trimethyl phosphorodithioate; D012701:Serotonin; D011700:Putrescine