Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo.

@article{Petri2003AbsorptionmetabolismOS,
  title={Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo.},
  author={Niclas Petri and Christer Tannergren and Birgit Holst and Fred A. Mellon and Yongping Bao and Geoffrey W. Plumb and J. Richard Bacon and Kathleen A. O'Leary and Paul A. Kroon and Lars Knutson and Patrik Forsell and Thomas Eriksson and Hans Lennernas and Gary Williamson},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2003},
  volume={31 6},
  pages={
          805-13
        }
}
For the first time the human intestinal effective permeability, estimated from the luminal disappearance and intestinal metabolism of phytochemicals, sulforaphane and quercetin-3,4'-glucoside, as well as the simultaneous changes in gene expression in vivo in enterocytes, has been studied in the human jejunum in vivo (Loc-I-Gut). Both compounds as components of an onion and broccoli extract could readily permeate the enterocytes in the perfused jejunal segment. At the physiologically relevant… 

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References

SHOWING 1-10 OF 42 REFERENCES

Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2.

TLDR
The occurrence of hydrolysis enhances the efficiency of intestinal absorption and metabolic conversion of dietary quercetin glucosides and lipophilicity of Q4'G was found to be higher than that of Q3G or Q3, 4'G, which suggests that lipophILicity contributes to the relatively efficient absorption of Q5'G.

The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans.

TLDR
Ketoconazole did not affect the jejunal Peff of (R/S)-verapamil, but it did increase the overall transport into the systemic circulation (bioavailability), probably by inhibition of the gut wall metabolism of verapamils.

Deglycosylation by small intestinal epithelial cell β-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans

TLDR
The absorption of dietary flavonoid glycosides in humans involves a critical deglycosylation step that is mediated by epithelial β-glucosidases (LPH andCBG), indicating a role of human LPH and CBG from small intestine in flavonoids absorption and metabolism.

Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases.

TLDR
Regioselectivity is dependent on the model flavonoid of interest, glucuronidation of luteolin and quercetin not following the same pattern, depending on the isoenzyme of UDP-glucuronosyltransferases (UGT), and the human intestine UGT's appear to be especially effective in conjugating this 3',4' catechol unit.

High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate.

TLDR
It is shown that the accumulated sulphoraphane was rapidly exported mainly in the form of GSH conjugate (GS-SF) in cultured human cells, indicating that to sustain the intracellular accumulation levels required a continuous uptake of SF to offset the rapid export of SF/ GS-SF.

Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates.

TLDR
It is concluded that SFN undergoes metabolism by S-oxide reduction and dehydrogenation and that GSH conjugation is the major pathway by which the parent compound and its phase I metabolites are eliminated in the rat.

Disposition of Glucosinolates and Sulforaphane in Humans After Ingestion of Steamed and Fresh Broccoli

TLDR
Results of this study indicate that the bioavailability of ITCs from fresh broccoli is approximately three times greater than that from cooked broccoli, in which myrosinase is inactivated.

Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin

TLDR
It is shown that quercetin glucosides are not present in plasma of human subjects 1.5 h after consumption of onions (a rich source of flavonoid glucoside), and the existence of substitutions in the B and/or C ring of plasma quercets suggests that these conjugates will each have very different biological activities.

Glutathione S-transferase in mucus of rat small intestine.

TLDR
The presence of this detoxication enzyme in the extracellular mucus layer provides a novel mechanism for preventing direct contact of potentially toxic dietary electrophiles with the intestinal enterocytes.