RESUMEN
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.
Asunto(s)
Genisteína/sangre , Genisteína/farmacocinética , Isoflavonas/sangre , Isoflavonas/farmacocinética , Vena Porta , Animales , Disponibilidad Biológica , Dieta , Heces/química , Genisteína/administración & dosificación , Mucosa Intestinal/metabolismo , Isoflavonas/administración & dosificación , Cinética , Masculino , Ratas , Ratas Wistar , Proteínas de Soja/químicaRESUMEN
Genistein and daidzein receive much attention because of their potential to prevent hormone-related cancer and cardiovascular diseases. Limited information is available on the pharmacokinetics of these compounds like, for instance, intestinal uptake by humans and systematic bioavailability. In this study the transport and metabolism of genistein, daidzein and their glycosides has been compared in various cellular models for intestinal absorption such as human colonic Caco-2, rat small intestinal IEC-18 and human immortalized colon HCEC cell lines. Genistein and daidzein were taken up by Caco-2, IEC-18 and HCEC cells and transported to almost same rate and extents. Glycosides were transported across IEC-18 and HCEC monolayers, but not across Caco-2 cells. In Caco-2 and IEC-18 cells, the glycosides were metabolized to their respective aglycones. Furthermore, it was shown that genistein and daidzein were glucuronidated and sulfated in Caco-2 cells, to glucuronidated forms in IEC-18 cells and to sulfated conjugates in HCEC cells. The results of this study compared with reported in vivo data indicate that Caco-2 cells are a valuable model for studying intestinal transport and metabolism of isoflavones.
RESUMEN
Genistein receives much attention because of its potential to prevent hormone-related cancer and cardiovascular diseases. Limited information is available on the pharmacokinetics of this compound like, for instance, their intestinal uptake by humans and systematic bioavailability. In this study, the fate of the absorption of genistein and its glycoside has been analysed in various isolated perfused gut segments of the rat. In all perfused gut segments the transport of genistein was higher compared to its glycoside. Furthermore, it appeared that the resorbate (i.e. serosal side) concentration of genistein was the highest in ileac segments, whereas the transport of genistein in the various other segments tested showed no difference between intestinal compartments. Less than 0.2% of genistin appeared in the resorbate fluid of all isolated gut segments. The main site of metabolism of genistein and its glycoside appears to be located in the jejunal compartment of the rat gut. About 38% of genistein and about 29% of genistin metabolised within 2h of perfusion. In the ileac and colonic intestinal segments, genistein metabolised for only 10%. For the first time, this study demonstrated that genistin could be metabolised by epithelial cells present in isolated colonic segments. However, the metabolites of genistin did not occur at the serosal side (the resorbate) of isolated colonic segments. We assume that there is no absorption of genistin and/or its metabolites in or through colonic tissue of the rat.