Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Parent, R. A.
Right arrow Articles by Sharp, D. E.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Parent, R. A.
Right arrow Articles by Sharp, D. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1998 Oxford University Press

other

Metabolism and Distribution of [2,3-14C]Acrolein in Sprague-Dawley Rats

II. Identification of Urinary and Fecal Metabolites1

Richard A. Parent*, Douglas E. Paust{dagger}, Margaret K. Schrimpf{dagger}, Rasmy E. Talaat{dagger},2, Rebecca A. Doane{ddagger}, Halina E. Caravello{ddagger}, Sung J. Lee§ and Dale E. Sharp{dagger},3

* Consultox, Limited, P.O. Box 1239, Damariscotta, Maine 04543-1239 {dagger}Covance Laboratories-Madison P.O. Box 7545, Madison, Wisconsin 53707 {ddagger}Baker Petrolite, Inc. P.O. Box 27714, Houston, Texas 77227-7714 §Biofor, Ltd. P.O. Box 629, Waveriy, Pennsylvania 18471, USA

Received January 20, 1998; accepted March 30, 1998

The metabolites of [2,3-14C]acrolein in the urine and feces of Sprague-Dawley rats were identified after either intravenous administration in saline at 2.5 mg/kg or oral administration by gavage as an aqueous solution as either single or multiple doses at 2.5 mg/kg or as a single dose of 15 mg/kg. Selected urine and feces samples were pooled by sex and collection interval and profiled by combinations of reverse-phase, anion-exchange, cation-exchange, and ion-exclusion high-performance liquid chromatography (HPLC). Feces were also profiled by size-exclusion chromatography. Metabolites were identified by comparison with well-characterized standards by HPLC and by mass spectrometry. The urinary metabolites were identified as oxalic acid, malonic acid, N-acetyl-S-2-carboxy-2-hydroxyethylcysteine, N-acetyl-S-3-hydroxypropylcysteine, N-acetyl-S-2-carboxyethylcysteine, and 3-hydroxypropionic acid. The fecal radioactivity from the oral dose groups was partitioned into methanol-soluble, water-soluble, and insoluble radioactivity, some of which could be liberated by dilute acid hydrolysis. HPLC analysis of these extracts revealed no discrete metabolites. Size-exclusion chromatography indicated a molecular weight range of 2,000 to 20,000 Da for the radioactivity, which was unaffected by hydrolysis at reflux with 6 M acid or base. This radioactivity was thought to be a homopolymer of acrolein, which was apparently formed in the gastrointestinal tract The pathways of acrolein metabolism were epoxidation followed by conjugation with glutathione, Michael addition of water followed by oxidative degradation, and glutathione addition to the double bond either following or preceding oxidation or reduction of the aldehyde. The glutathione adducts were further metabolized to the mercapturic acids.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.