Metabolism of [14C]- and [35S]S-(1,2-dichlorovinyl)-L-cysteine in the male Fischer 344 rat. 1995

M B Finkelstein, and N J Patel, and M W Anders
Department of Pharmacology, University of Rochester, NY 14642.

The metabolic fate, tissue distribution, and elimination profile of [35S]- and [cysteine-U-14C]S-(1,2-dichlorovinyl)-L-cysteine (DCVC)--given either intravenously or intraperitoneally to male Fischer 344 rats--was investigated. Blood samples were collected periodically from 5 min to 96 hr after administration. More than 99% of the DCVC was cleared from plasma within 2.5 hr after either intravenous or intraperitoneal injection. The initial half-lives of both [35S]- and [14C]DCVC were 2.0 and 2.8 hr, respectively, and the mercapturate S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine was detected in plasma within 5 min of giving DCVC. The major plasma metabolite detected after giving [35S]DCVC was inorganic sulfate, and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine and pyruvate were also detected in plasma after giving [14C]DCVC. S-(1,2-Dichlorovinyl)-N-acetyl-L-cysteine was the major urinary metabolite detected after giving [14C]DCVC, and inorganic sulfate was excreted in the urine after giving [35S]DCVC. Administration of the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid led to a significant increase in the urinary excretion of radioactivity, mostly in the form of the mercapturate. The kidney contained the highest amount of radioactivity after administration of [35S]DCVC. In addition, similar amounts of radioactivity were present in brain, heart, kidney, and liver after administration of [14C]DCVC, but the 14C content of the liver was decreased in aminooxyacetic acid-treated rats. This study shows that DCVC is rapidly metabolized to inorganic sulfate and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine, which are eliminated in the urine.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008297 Male Males
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000625 Aminooxyacetic Acid A compound that inhibits aminobutyrate aminotransferase activity in vivo, thereby raising the level of gamma-aminobutyric acid in tissues. Aminooxyacetate,Carboxymethoxyamine,Acid, Aminooxyacetic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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