thiourea and diethyl-maleate

Topics: Acetylcysteine; Animals; Female; Glutathione; Liver; Lung; Male; Maleates; Rats; Thiourea

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.

Topics: Acetylglucosaminidase; Animals; Blood Urea Nitrogen; Buthionine Sulfoximine; Cisplatin; Enzymes; Free Radical Scavengers; gamma-Glutamyltransferase; Glutathione; Kidney Cortex; Male; Maleates; Methionine Sulfoximine; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Thiourea

The acute toxicity of 2-thiotriazone (TTZ) was evaluated in adult and immature rats of both sexes. 2-Thiotriazone produced marked pulmonary toxicity in rats that was both age and sex dependent. TTZ was highly toxic to adult male rats when given as a single dose (oral LD50 = 4.6 mg/kg and ip LD50 = 1.4 mg/kg) with 100% mortality being observed at 10 mg/kg orally and 5 mg/kg intraperitoneally (ip). Female rats were more resistant than males with only 40% mortality at concentrations of 10-100 mg/kg orally. Immature rats (30-40 days of age) of both sexes showed no response when TTZ was administered at concentrations of 10-1000 mg/kg either orally or ip. Gross and histological examination of lung tissue from rats affected by TTZ revealed severe pulmonary edema, effusion, and mottling of the lungs. Significant increases in lung weights were also observed. Studies with diethylmaleate (DEM) and TTZ indicated that DEM pretreatment potentiated the toxic effects of TTZ in adult male, adult female, and immature rats. Lung weights in DEM/TTZ-treated rats were twice that of animals treated with TTZ alone. The results of the present study indicate that TTZ is highly toxic to male rats with the lungs being particularly vulnerable to its effects and that TTZ toxicity is enhanced by DEM pretreatment.

Topics: Animals; Drug Synergism; Female; Fertilizers; Lung; Male; Maleates; Organ Size; Rats; Rats, Inbred Strains; Thiourea