diethyl-maleate and Carbon-Tetrachloride-Poisoning

We have shown that urinary taurine level may be used as a biomarker of pathological and biochemical lesions. Detection of changes in the urinary concentration of this low molecular weight metabolite indicates biochemical lesions which may also be associated with pathological damage. Hepatotoxic compounds such as CCl4, galactosamine and thioacetamide that cause hepatic necrosis and compounds such as hydrazine and ethionine that cause fatty liver all result in elevated urinary taurine levels in rats. However compounds which do not cause liver damage, such as cycloheximide, also raise urinary taurine levels. All of these substances are known to or are believed to inhibit protein synthesis. Conversely, compounds which increase protein synthesis, such as phenobarbital and clenbuterol, significantly decrease urinary taurine levels. Compounds which interfere with hepatic GSH synthesis will also change urinary taurine levels. Thus, depletion of GSH with diethyl maleate or phorone decreases urinary taurine whereas inhibition of GSH synthesis with compounds such as buthionine sulphoximine increases urinary taurine levels. In isolated hepatocytes in vitro, leakage of taurine occurs in response to cytotoxic compounds such as hydrazine and allyl alcohol. However, total taurine levels were increased by the hepatotoxicant CCl4. Taurine synthesis is decreased by depletion of GSH with allyl alcohol in isolated hepatocytes. Therefore taurine levels are an important potential biomarker for biochemical lesions induced by chemicals both in vivo and in vitro, in particular changes in protein and GSH synthesis.

Topics: Animals; Biomarkers; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Cells, Cultured; Clenbuterol; Galactosamine; Glutathione; Ketones; Liver; Liver Diseases; Male; Maleates; Necrosis; Phenobarbital; Rats; Rats, Sprague-Dawley; Taurine; Thioacetamide

A simple rapid determination of glutathione (GSH) and cytoplasmic protein bound SH groups (PBSH), appropriate to study their relationship in tissues, in rat liver, kidney and testis was developed. Hepatic GSH and PBSH were measured after treatment with methyl iodide (400, 800 mg/kg, after 0.5 h), diethyl maleate (2 ml/kg, after 1h), carbon tetrachloride (1.2 ml/kg, after 3 h), phenobarbital (80 mg/kg for 3 days). Methyl iodide and diethyl maleate showed a decrease of GSH and PBSH; after treatment with phenobarbital an increase of GSH and PBSH was observed; no decrease of GSH and PBSH was found after carbon tetrachloride intoxication.

Topics: Animals; Carbon Tetrachloride Poisoning; Cytoskeletal Proteins; Glutathione; Hydrocarbons, Iodinated; Liver; Maleates; Methods; Phenobarbital; Rats; Rats, Inbred Strains; Sulfhydryl Compounds

Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH) following an intragastric administration of carbon tetrachloride (CCl4) to rats. Oxidized glutathione (GSSG) also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2.), glutathione peroxidase (EC 1.11.1.9) and malic enzyme (EC 1.1.1.40) activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Glucosephosphate Dehydrogenase; Glutathione; Liver; Male; Maleates; Oxidation-Reduction; Phosphogluconate Dehydrogenase; Rats; Rats, Inbred Strains

Topics: Aminopyrine N-Demethylase; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Glutathione; Kinetics; Liver; Male; Maleates; Microsomes, Liver; Nitroanisole O-Demethylase; Rats

Topics: Animals; Antimetabolites; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cytosol; Glutathione Transferase; In Vitro Techniques; Liver; Maleates; Rats; Time Factors