N-acetylcysteine-conjugated pyrrole identified in rat urine following administration of two pyrrolizidine alkaloids, monocrotaline and senecionine.
This report demonstrates that an Ehrlich-reagent-positive metabolite of monocrotaline and senecionine is excreted in the urine of male rats as an N-acetylcysteine conjugate of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (NAC-DHP). Isolation of the metabolite employed an initial organic extraction followed by HPLC separation of remaining urinary components using a reverse-phase, polymer-based, PRP-1 column. Fast-atom-bombardment tandem mass spectrometry was used to identify the metabolite. This finding suggests that reactive metabolites of pyrrolizidine alkaloids generated in the liver can survive the aqueous environment of the circulatory system as glutathione conjugates or mercapturic acids.
Estep
J E
JE
Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
Lamé
M W
MW
Jones
A D
AD
Segall
H J
HJ
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains
D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; C066467:N-acetylcysteine-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine; D016686:Monocrotaline; C009237:senecionine; D000111:Acetylcysteine