Increases in urinary enzyme excretion in rats depleted of glutathione inhibited by scavenger of oxygen free radicals.
Urinary excretion of enzymes by rats was assessed after glutathione (GSH) was depleted by treatment with a mixture of the GSH depletors D,L-buthionine-S,R-sulfoximine (BSO) and diethylmaleate (DEM). Renal GSH was low 2 h after treatment and later returned to the control level. The urinary excretion of gamma-glutamyltranspeptidase (gamma-GTP) and N-acetyl-beta-D-glucosaminidase (NAG) remained high for at least 3 d after the injection of BSO (100 mg/kg) and DEM (0.5 ml/kg), with no effect on the blood urea nitrogen level. N,N'-Dimethylthiourea (DMTU), a scavenger of oxygen free radicals, inhibited this increase in the urinary excretion of gamma-GTP. DMTU also inhibited the increase in cisplatin-induced NAG excretion caused by the GSH depletors. These results suggested that the urinary excretion of these enzymes is an index of renal tubular injury caused by short-term depletion of renal GSH, and that the generation of free radicals may be involved in renal tubular injury during GSH depletion or caused by cisplatin together with GSH depletors.
Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
M
M
Gemba
T
T
Yamaguchi
K
K
Kambara
A
A
Suzuki
Y
Y
Kawai
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000494:pharmacology; D004798:Enzymes / Q000652:urine*; D016166:Free Radical Scavengers; D005978:Glutathione / Q000502:physiology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000652:urine
D004798:Enzymes; D016166:Free Radical Scavengers; D008298:Maleates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C038983:1,3-dimethylthiourea; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; C014476:diethyl maleate; D005978:Glutathione; D013890:Thiourea; D002945:Cisplatin