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.