Pulmonary toxicity of thioureas in the rat.
Administration of alpha-naphthylthiourea (ANTU) to rats causes damage to pulmonary endothelial cells and possibly mesothelial lining cells that together may account for the massive pleural effusion characteristic of thiourea toxicity. Using 35S-thiourea as a model compound, the extent of binding of 35S to lung proteins correlated well with the extent of edema, suggesting that the extent of binding of thiourea metabolites is a measure of lung toxicity. ANTU and phenylthiourea (PTU) compete for 35S binding to lung slices, suggesting that these toxins may act in a similar way. Binding of 35S in lung slices from resistant rats is much less than in controls, and resistance cannot be explained by differences in either whole body metabolism or redistribution of thiourea in vivo. Lung glutathione levels (in vitro and in vivo) in normal and resistant rats following thiourea administration were essentially the same. However, at doses of thiourea that cause pleural effusion, there was an increase in total lung glutathione.
Scott
A M
AM
Department of Biochemistry, University College Cardiff, UK.
Powell
G M
GM
Upshall
D G
DG
Curtis
C G
CG
D000818:Animals; D001667:Binding, Competitive; D004351:Drug Resistance; D004727:Endothelium / Q000032:analysis / Q000187:drug effects / Q000648:ultrastructure; D005978:Glutathione / Q000032:analysis; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008648:Mesoderm / Q000032:analysis / Q000187:drug effects / Q000648:ultrastructure; D011485:Protein Binding; D051381:Rats; D012378:Rodenticides / Q000378:metabolism* / Q000633:toxicity; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity
D012378:Rodenticides; D005978:Glutathione; D013890:Thiourea; C005277:alpha-naphthyl thiourea