Toxic effects of dimethylthiourea in rats.
Dimethylthiourea (DMTU) is a small, highly diffusible molecule that effectively scavenges toxic oxygen metabolites in vitro and reduces oxidative injury in many biologic systems. Nonetheless, for unknown reasons, DMTU has occasionally failed to decrease damage in some systems where injury is presumed to be mediated by oxygen metabolites. We hypothesized that the inconsistent pattern of protection might partially reflect a direct toxicity of DMTU. Our results supported this premise. We found that rats treated with commonly used doses of highly purified DMTU had increased lung accumulation of intravenously injected iodine 125-labeled albumin (4 hours after DMTU treatment) and decreased blood glutathione levels (24 hours after DMTU treatment) when compared with saline-injected control rats. In contrast, rats treated with dimethylurea, a analog of DMTU, did not develop increased accumulation of labeled albumin in the lungs or decreased blood glutathione levels. We conclude that DMTU has intrinsically toxic effects in rats and that DMTU toxicity may at times obscure its protective action.
Beehler
C J
CJ
Webb-Waring Lung Institute, University of Colorado Health Sciences Center, Denver.
Ely
M E
ME
Rutledge
K S
KS
Simchuk
M L
ML
Reiss
O K
OK
Shanley
P F
PF
Repine
J E
JE
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008782:Methylurea Compounds / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin; D013270:Stomach / Q000473:pathology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000633:toxicity
D008782:Methylurea Compounds; D012709:Serum Albumin; C038983:1,3-dimethylthiourea; D005978:Glutathione; D013890:Thiourea; C018275:1,1-dimethylurea