Influence of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the urinary elimination of mercapturic acids of ethylene oxide, dibromoethane, and acrylonitrile: a dose-effect study.
Metabolic disposition of ethylene oxide, dibromoethane, and acrylonitrile in rats after acute exposure was studied by examining the relationship between dose and urinary metabolites, and by establishing the influence of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the above relationship. Respective urinary metabolites, hydroxyethylmercapturic acid, cyanoethylmercapturic acid, thiocyanate, and ethylene glycol, were quantified to estimate the extent to which each compound was metabolized. The animals were given either ethylene oxide (0.34, 0.68, or 1.36 mmol/kg), dibromoethane (0.2, 0.4, or 0.6 mmol/kg), or acrylonitrile (0.10, 0.38, or 0.76 mmol/kg). Urine samples were collected at 24 h. The metabolic biotransformation of all three chemicals to their respective mercapturic acids was strongly indicative of saturable metabolism. Administration of OCTA (4-5 mmol/kg) enhanced gluthathione availability and increased excretion of urinary mercapturic acids at the higher doses of the chemicals. This study indicates that OTCA increases the capacity for detoxification via the glutathione pathway thereby partially correcting the nonlinearity between the administered dose of ethylene oxide, dibromoethane, and acrylonitrile and the amount of certain urinary metabolites.
Goyal
R
R
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.
Tardif
R
R
Brodeur
J
J
D000111:Acetylcysteine / Q000652:urine*; D000181:Acrylonitrile / Q000652:urine*; D000818:Animals; D015946:Ethylene Dibromide / Q000652:urine*; D005027:Ethylene Oxide / Q000652:urine*; D005978:Glutathione / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000652:urine*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009570:Nitriles / Q000652:urine*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013997:Time Factors
D006842:Hydrocarbons, Brominated; D009570:Nitriles; D013844:Thiazoles; D053778:Thiazolidines; D015946:Ethylene Dibromide; D005978:Glutathione; D005027:Ethylene Oxide; D000181:Acrylonitrile; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid