The present study describes an in vivo bioavailability experiment for genistein and its glycoside genistin, either as pure compounds or from a soy protein isolate extract, using freely moving unanesthetized rats with a cannulation in the portal vein. The results show that genistein is readily bioavailable, being observed in portal vein plasma at the first point of detection at 15 min after dosing. The AUC(0-24h) values for total genistein and its conjugates were 54, 24, and 13 microM h for genistein, genistin, and an enriched protein soy extract, respectively. These results indicate that the bioavailability of genistein is higher for the aglycon than for its glycoside. Genistin is partly absorbed in its glycosidic form. It is concluded that bioavailability studies based on portal vein plasma levels contribute to insight into the role of the intestine and liver in deglycosylation and uptake characteristics of glycosylated flavonoids.

1. The metabolism of 50 microM 7-ethoxycoumarin and 50 microM [3-14C]coumarin has been studied in precision-cut liver slices from the male Sprague-Dawley rat, female DBA/2 mouse, male Dunkin-Hartley guinea pig, male Cynomolgus monkey and man. 2. In liver slices from all five species 7-ethoxycoumarin was metabolized to 7-hydroxycoumarin (7-HC), which was extensively conjugated with D-glucuronic acid and sulphate. In rat and mouse, 7-HC was preferentially conjugated with sulphate, whereas rates of glucuronidation and sulphation were similar in the other three species. 3. [3-14C]coumarin was metabolized by liver slices from all five species to various polar products and to metabolite(s) that bound covalently to liver slice proteins. In Cynomolgus monkey and both human subjects studied, 7-HC was the major metabolite that was conjugated with D-glucuronic acid and sulphate, whereas in rat the major metabolites were products of the 3-hydroxylation pathway and unknown metabolites. Major metabolites in mouse liver slices were 7-HC, 3-hydroxylation pathway products and unknown metabolites, and in guinea pig liver slices, 7-HC and unknown metabolites. 4. The metabolism of 7-ethoxycoumarin to free and conjugated 7-HC and [3-14C]coumarin to total polar products was greater in liver slices from mouse and Cynomolgus monkey than the other three species. 5. With liver slices from all five species there appeared to be little difference in the extent of metabolism of 7-ethoxycoumarin and [3-14C]coumarin to various products in either a complex tissue culture medium (RPMI 1640 plus foetal calf serum) or a simple balanced salt solution (Earle's balanced salt solution). 6. These results demonstrate that precision-cut liver slices are a valuable in vitro model system for investigating species differences in xenobiotic metabolism. Generally, the observed species differences in coumarin metabolism in vitro agree well with available in vivo data.

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