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

Abstract

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.