Comparison of the metabolism of 7-ethoxycoumarin and coumarin in precision-cut rat liver and lung slices

The metabolism of 7-ethoxycoumarin and [3- 14C] coumarin was compared in precision-cut rat liver and lung slices. The lung slices were prepared using an agarose gel instilling technique enabling the production of tissue cylinders followed by lung slices employing a Krumdieck tissue slicer. Both 50μM...

Full description

Saved in:
Bibliographic Details
Published in:Food and chemical toxicology 1995-03, Vol.33 (3), p.233-237
Main Authors: Price, R.J., Renwick, A.B., Beamand, J.A., Esclangon, F., Wield, P.T., Walters, D.G., Lake, B.G.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
coumarins
Coumarins - metabolism
Coumarins - toxicity
Culture Techniques
Glucuronates - metabolism
Glucuronic Acid
Isotope Labeling
liver
Liver - drug effects
Liver - metabolism
Liver - pathology
Lung - drug effects
Lung - metabolism
Lung - pathology
lungs
Male
Medical sciences
metabolism
Plant poisons toxicology
Rats
Rats, Sprague-Dawley
Sulfates - metabolism
toxicity
Toxicology
Umbelliferones - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The metabolism of 7-ethoxycoumarin and [3- 14C] coumarin was compared in precision-cut rat liver and lung slices. The lung slices were prepared using an agarose gel instilling technique enabling the production of tissue cylinders followed by lung slices employing a Krumdieck tissue slicer. Both 50μM 7-ethoxycoumarin and 50μM [3- 14C]coumarin were metabolized by rat liver and lung slices. 7-Ethoxycoumarin was converted to 7-hydroxycoumarin (7-HC) which was conjugated with both d-glucuronic acid and sulfate. 7-HC sulfate was the major metabolite formed by both liver and lung slices. [3- 14C]Coumarin was metabolized by rat liver and lung slices to both polar products and to metabolite(s) that bound covalently to tissue slice proteins. The polar products included unidentified metabolites and 3-hydroxylation pathway products, with only very small quantities of 7-HC being formed. These results demonstrate that precision-cut lung slices area useful model in vitro system for studying the pulmonary metabolism of xenobiotics. Moreover, the precision-cut tissue slice technique may be employed for comparisons of hepatic and extrahepatic xenobiotic metabolism.
ISSN:0278-6915
1873-6351
DOI:10.1016/0278-6915(94)00129-C