Rj. Price et al., COMPARISON OF THE METABOLISM OF 7-ETHOXYCOUMARIN AND COUMARIN IN PRECISION-CUT RAT-LIVER AND LUNG SLICES, Food and chemical toxicology, 33(3), 1995, pp. 233-237
The metabolism of 7-ethoxycoumarin and [3-C-14]coumarin was compared i
n precision-cut rat liver and lung slices. The lung slices were prepar
ed using an agarose gel instilling technique enabling the production o
f tissue cylinders followed by lung slices employing a Krumdieck tissu
e slicer. Both 50 mu M 7-ethoxycoumarin and 50 mu M [3-C-14]coumarin w
ere metabolized by rat liver and lung slices. 7-Ethoxycoumarin was con
verted to 7-hydroxycoumarin (7-HC) which was conjugated with both D-gl
ucuronic acid and sulfate. 7-HC sulfate was the major metabolite forme
d by both liver and lung slices. [3-C-14]Coumarin was metabolized by r
at liver and lung slices to both polar products and to metabolite(s) t
hat bound covalently to tissue slice proteins. The polar products incl
uded unidentified metabolites and 3-hydroxylation pathway products, wi
th only very small quantities of 7-HC being formed. These results demo
nstrate that precision-cut lung slices are a useful model in vitro sys
tem for studying the pulmonary metabolism of xenobiotics. Moreover, th
e precision-cut tissue slice technique may be employed for comparisons
of hepatic and extrahepatic xenobiotic metabolism.