Role of glutathione metabolism in the reduction of proteinuria by dimethylthiourea in adriamycin nephrosis.
Glutathione (GSH) metabolism, a tissue detoxification pathway, was evaluated in rats with adriamycin nephrosis (AN) treated with dimethylthiourea (DMTU), a free radical scavenger. After 7 days of DMTU, a significant reduction in proteinuria occurred as compared to AN controls (62.4 +/- 13.3 vs. 155.0 +/- 24.0 mg/24 h). A significant increase in renal cortical GSH content as well as glutathione peroxidase (GP) and transferase (GT) activities occurred in DMTU-treated rats as compared to controls. Glutathione monoethyl ester (GME) administration alone reduced proteinuria by 21% in AN, which was not significant despite a large increase in the renal GSH content, however, GP and GT activities were not increased by GME. We conclude that DMTU ameliorates glomerular injury in AN by stimulating GSH metabolism.
Milner
L S
LS
Department of Pediatrics, University of Nebraska Medical Center, Omaha.
Wei
S H
SH
Stohs
S J
SJ
Eldeen
Z M
ZM
Houser
M T
MT
D000818:Animals; D004317:Doxorubicin; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
C042431:S-ethyl glutathione; D004317:Doxorubicin; C038983:1,3-dimethylthiourea; D005978:Glutathione; D013890:Thiourea