Intestinal Uptake and Biliary Excretion of the Isoflavone Genistein in Rats , ,

Abstract

The intestinal absorption, biliary excretion and metabolism of genistein, a potent and specific protein tyrosine kinase inhibitor that occurs naturally in soy foods, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas. 4-14C-Genistein, when infused into the duodenum, was rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-beta-glucuronide conjugate. Cumulative recovery of 14C-radioactivity in the bile over a 4-h period was 70-75% of the dose. When genistein was infused into the portal vein, it was also taken up efficiently by the liver, conjugated with glucuronic acid and transported into bile. However, portal blood collected after duodenal infusions of genistein contained mostly genistein 7-O-beta-glucuronide, suggesting that in vivo glucuronidation occurred in the intestinal wall rather than the liver. This was confirmed using everted intestinal sac preparations. Reinfusion of genistein 7-O-beta-glucuronide into the duodenum or into the mid small intestine resulted in its reappearance in the bile, albeit more slowly than when genistein was infused. Over a 4-h collection period, the cumulative recovery of 14C-radioactivity in bile was 27 and 70-75% of the administered dose for duodenal and ileal infusions, respectively. These data indicate that genistein is highly bioavailable in rats and because of its enterohepatic circulation may accumulate within the gastrointestinal tract.

The splanchnic metabolism of flavonoids highly differed according to the nature of the compound

“…When flavonoid metabolites resulting from intestinal conjugation are secreted in the mesenteric vein, a proportion of them are taken up and metabolized by the liver (3,4,26) and then partially secreted in the bile (20,34,44,45). In our experiments, the presence of flavonoids in the bile for all the tested compounds indicated that whatever their origin, flavonoids undergo enterohepatic cycling.…”

“…Some of them, such as catechin, are sparingly secreted in the bile (1%), whereas others, like genistein and eriodictyol, are extensively recycled (32 and 23% of the perfused dose, respectively). The importance of the biliary secretion in genistein bioavailability was previously suggested in a study reporting that 70-75% of genistein perfused in the small intestine was recovered in the bile over 4 h of perfusion (34). By contrast, the biliary secretion of quercetin and catechin appears quite limited, indicating that the biliary pathway probably plays a minor role in their elimination.…”

Effects of Intestinal Flora on the Metabolism and Absorption of Isoflavones

“…When 4-14 Cgenistein is infused into the duodenum of rats, it is rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-β-glucuronide conjugate 46 . Intestinal perfusion studies have indicated that some of the genistein glucuronide produced in the rat small intestine is returned to the lumen [4][5][6] .…”

Health potential of soy isoflavones for menopausal women

“…In addition, some of the metabolic products of isoflavones, in particular equol, may be transported in blood weakly associated with serum proteins. Equol, and possibly other isoflavones, are secreted by liver into bile and they therefore can cycle as part of the enterohepatic circulation 13,14 . This cycling may occur several times over one or more days and allows a steady-state concentration of these molecules to develop in blood as long as the intake of soy foods continues on a daily basis.…”