Liver glutathione depletion induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis.

The mechanisms of bromobenzene and iodobenzene hepatotoxicity in vivo were studied in mice. Both the intoxications caused a progressive decrease in hepatic glutathione content. In both instances liver necrosis was evident only when the hepatic glutathione depletion reached a threshold value (3.5-2.5 nmol/mg protein). The same threshold value was evident for the occurrence of lipid peroxidation. Similar results were obtained in a group of mice sacrificed 15-20 hours after the administration of diethylmaleate, a drug which is mainly conjugated with hepatic glutathione without previous metabolism. The correlation between lipid peroxidation and liver necrosis was much more significant than that between covalent binding and liver necrosis. This fact supports the view that lipid peroxidation is the major candidate for the liver cell death produced by bromobenzene intoxication. Moreover, a dissociation of liver necrosis from covalent binding was observed in experiments in which Trolox C (a lower homolog of vitamin E) was administered after bromobenzene poisoning. The treatment with Trolox C, in fact, almost completely prevented both liver necrosis and lipid peroxidation, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein.

[Urinary enzymes in the non-invasive diagnosis of kidney epithelial lesions in acute kidney failure]. / Harnenzyme zur nichtinvasiven Diagnostik von Nierenepithelschäden im akuten Nierenversagen.

The present investigation describes the urinary output of four different enzymes localized within nephron cells in two models of experimental acute renal failure. The activities of fructose-1,6-diphosphatase (FDP), glutathione-S-transferase (GST), N-acetyl-beta-D-glucosaminidase (NAG) and pyruvate kinase (PK) were determined in the urine of rats after maleate or HgCl2 intoxication. 2 hours after maleate intoxication the urinary output of FDP, GST and NAG was significantly increased above control values. 6 hours after HgCl2 poisoning FDP, GST and NAG showed increased urinary enzyme activities. The urinary activity of each enzyme was significantly increased 24 hours after intoxication. These results are in good accordance with the damage observed on light and electron microscopic investigations carried out with both experimental models. Furthermore, general problems of urinary enzyme measurements are discussed in this paper.