Comparison of the metabolism of 7-ethoxycoumarin and coumarin in precision-cut rat liver and lung slices.
The metabolism of 7-ethoxycoumarin and [3-(14)C]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 50 microM 7-ethoxycoumarin and 50 microM [3-(14)C]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-(14)C]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 are a 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.
Price
R J
RJ
BIBRA International, Carshalton, Surrey, UK.
Renwick
A B
AB
Beamand
J A
JA
Esclangon
F
F
Wield
P T
PT
Walters
D G
DG
Lake
B G
BG
D000818:Animals; D003374:Coumarins / Q000378:metabolism* / Q000633:toxicity; D046508:Culture Techniques; D005965:Glucuronates / Q000378:metabolism; D020723:Glucuronic Acid; D007553:Isotope Labeling; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism; D014468:Umbelliferones / Q000378:metabolism
D003374:Coumarins; D005965:Glucuronates; D013431:Sulfates; D014468:Umbelliferones; C017299:7-ethoxycoumarin; C031477:7-hydroxycoumarin; D020723:Glucuronic Acid; C030123:coumarin