diethyl-maleate and methyl-iodide

Previous studies have suggested a significant role for reproductive tract glutathione in protecting against chemical-induced germ-cell mutations. Therefore, a number of compounds were tested for their ability to perturb glutathione levels in the testes and epididymides as well as liver following single acute dosages to rats. Phorone (250 mg/kg), isophorone (500 mg/kg), and diethyl maleate (500 mg/kg) significantly reduced glutathione in the liver and in both reproductive organs examined. Methyl iodide (100 mg/kg), trimethyl phosphate (600 mg/kg), naphthalene (500 mg/kg), acetaminophen (1500 mg/kg), and pentachlorophenol (25 mg/kg) affected hepatic and epididymal glutathione, but had little or no effect on testicular levels. The ability of isophorone to enhance the covalent binding of tritiated ethyl methanesulfonate (3H-EMS) to spermatocytes was assessed. Perturbation of reproductive tract glutathione by isophorone treatment significantly enhanced the extent of 3H-EMS-induced binding to sperm heads. The temporal pattern of ethylations in sperm heads was consistent with the stage of sperm development known to be susceptible to ethylations by EMS. Therefore, chemical-induced lowering of glutathione in the male reproductive tract may be a mechanism for potentiation of chemical-induced germ-cell mutations.

Topics: Animals; Cyclohexanes; Cyclohexanones; Epididymis; Glutathione; Hydrocarbons, Iodinated; Ketones; Male; Maleates; Naphthalenes; Organophosphates; Rats; Rats, Inbred Strains; Testis

Topics: Animals; Bile; Biological Transport; Cyclohexanes; Cyclohexenes; Female; Glutathione; Hydrocarbons, Iodinated; Inactivation, Metabolic; Lead; Maleates; Rats

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

Blood and liver glutathione levels were measured under the effect of an acute exposure to high doses of glutathione-depleting substances. Among direct-acting glutathione-depleting substances, diethyl maleate (0.3, 0.7 and 1.4 ml kg-1) caused a marked reduction of both blood and liver glutathione, whereas methyl iodide (320 mg kg-1) led to a decrease in liver glutathione stores immediately and in blood stores with a longer latency. Indirectly glutathione-depleting substances, like paracetamol (0.5-1.0 g kg-1) and styrene (250 mg kg-1), caused a reduction of liver glutathione, but not a similar reduction of blood glutathione. Blood glutathione is not a good measure of organ glutathione stores when dealing with indirect-acting glutathione-depleting substances.

Topics: Acetaminophen; Animals; Glutathione; Hydrocarbons, Iodinated; Liver; Maleates; Rats; Toxicology