A SPECIES COMPARISON OF C-14-LABELED 7-ETHOXYCOUMARIN METABOLISM IN PRECISION-CUT LIVER SLICES FROM GUINEA-PIG AND DOG USING A PHOSPHOR IMAGING-SYSTEM

The metabolism of C-14-labeled 7-ethoxycoumarin (7EC) has been investi gated in precision-cut liver slices from guinea pigs and dogs. 7EC was incubated with slices in 12-well plates (4 slices/well; n = 3) for up to 8 hr. In addition, a new simple method was established for analyzi ng 7EC and its metabolites simultaneously by using thin-layer chromato graphy-radioluminography (TLC-RLG). In both species, 7EC was taken up rapidly into the slices and metabolized extensively under the conditio ns used (no serum fraction supplemented), showing both phase I and pha se II metabolism. In guinea pig medium samples, 4-ethoxy-2-hydroxyphen ylacetic acid (EHPA) and 7-hydroxycoumarin (7HC) glucuronide were majo r metabolites. In dogs, conjugated 7HCs (with D-glucuronic acid and su lfate) were major products but EHPA was formed only to a small extent. These results suggest that deethylation in dogs occurs to a much grea ter extent than in guinea pigs. These results demonstrate the advantag es of precision-cut liver slices as a powerful tool to investigate the species specific metabolism of xenobiotics, since the conditions empl oyed enabled both phase I and phase II reactions in vitro.