title: Identification of a cis-2-butene-1,4-dial-derived glutathione conjugate in the urine of furan-treated rats.
abstract: The hepatocarcinogen and toxicant furan requires metabolic activation to elicit its toxic effects. The available experimental evidence indicates that the overall metabolism of furan is initiated via cytochrome P450 catalyzed oxidation to cis-2-butene-1,4-dial. This alpha,beta-unsaturated dialdehyde reacts in vitro with protein and DNA nucleophiles. To determine if this compound is an in vivo intermediate in the metabolism of furan, rats were treated with either [(12)C(4)]furan or [(13)C(4)]furan, and urine was collected for 24 h. Capillary LC/MS/MS analysis of the urine indicated that one of the metabolites was a monoglutathione conjugate of cis-2-butene-1,4-dial. These results indicate that glutathione conjugation of the reactive metabolite of furan occurs in vivo. This metabolite may serve as a useful marker for furan exposure and metabolism in risk assessment studies.
authors.affiliation: Division of Environmental Health Sciences and the Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. peter431@umn.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Peterson
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Cummings
authors.forename: Jacqueline Y
authors.initials: JY
authors.lastname: Chan
authors.forename: Choua C
authors.initials: CC
authors.lastname: Vu
authors.forename: Brock A
authors.initials: BA
authors.lastname: Matter
mesh_terms: D000818:Animals; D005663:Furans / Q000008:administration & dosage*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051381:Rats
chemical_list: D005663:Furans; D005978:Glutathione; C039281:furan