Metabolism of [14C]- and [35S]S-(1,2-dichlorovinyl)-L-cysteine in the male Fischer 344 rat.
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.
Finkelstein
M B
MB
Department of Pharmacology, University of Rochester, NY 14642.
Patel
N J
NJ
Anders
M W
MW
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013431:Sulfates / Q000378:metabolism; D014018:Tissue Distribution
D013431:Sulfates; D000625:Aminooxyacetic Acid; C039961:S-(1,2-dichlorovinyl)cysteine; D003545:Cysteine