0000000000249352
AUTHOR
David G. Walters
Metabolism of [3-14C]coumarin to polar and covalently bound products by hepatic microsomes from the rat, Syrian hamster, gerbil and humans.
The metabolism of 0.19 and 2.0 mM-[3-14C]coumarin to polar products and covalently bound metabolites has been studied with hepatic microsomes from the rat, Syrian hamster, Mongolian gerbil and humans. [3-14C]Coumarin was metabolized by liver microsomes from all species to a number of polar products and to metabolite(s) that became covalently bound to microsomal proteins. The polar products included 3-, 5- and 7-hydroxycoumarins, o-hydroxyphenylacetaldehyde and o-hydroxyphenylacetic acid. Coumarin 7-hydroxylation was observed in all species except the rat. With 0.19 mM-[3-14C]coumarin, 7-hydroxycoumarin was the major metabolite in human liver microsomes, whereas in the other species with 0.1…
Metabolism of coumarin by precision-cut calf liver slices and calf liver microsomes.
1. The metabolism of 50 microM [3-14C]coumarin has been studied in precision-cut-calf liver slices. 2. The metabolism of 50 microM coumarin to 7-hydroxycoumarin has also been examined in calf, rat, Cynomolgus monkey and human liver microsomal preparations. 3. In precision-cut calf liver slices, [3-14C]coumarin was metabolized to various polar products and to metabolite(s) that bound covalently to calf liver slice proteins. The polar products included 7-hydroxycoumarin (which was extensively conjugated with D-glucuronic acid and/or sulphate), metabolites of the 3-hydroxylation pathway (mainly o-hydroxyphenylethanol and o-hydroxyphenylacetic acid), and unknown metabolites. 4. Coumarin 7-hydro…
Studies on the disposition, metabolism and hepatotoxicity of coumarin in the rat and Syrian hamster.
The hepatotoxicity, metabolism and disposition of coumarin has been compared in male Sprague-Dawley rats and Syrian hamsters. The treatment of rats for 12, 24 and 42 weeks with diets containing 0.2 and 0.5% coumarin resulted in hepatotoxicity and increased relative liver weights. While levels of cytochrome P450 (CYP) and CYP-dependent enzymes were decreased, levels of reduced glutathione (GSH) and activities of UDP glucuronosyltransferase, gamma-glutamyltransferase and GSH S-transferase were increased. In contrast, coumarin produced few hepatic changes in the Syrian hamster. Following a single oral dose of 25 mg/kg [3-14C]coumarin, radioactivity was rapidly excreted by the rat and Syrian ha…
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 metabol…