On Mar 19, 1:41 pm, ironjustice <ironjust...@cashette.com>
wrote:Cytochrome P450 inhibition? <<

A curious thing here is .. quercitin also inhibits Cytochrome P450 and
quercitin is a premiere iron chelator.

Sooo .. is it the flavonoids which the "studies show that fruit also
has benefit with citrus fruits
being particularly effective" ..?

Iron binding / chelating .. ?

Int J Pharm. 2006 Apr 26;313(1-2):144-9. Epub 2006 Mar 3. Links
Enhanced bioavailability of tamoxifen after oral administration of
tamoxifen with quercetin in rats.
Shin SC, Choi JS, Li X.
College of Pharmacy, Chonnam National University, Bukgu, Gwangju
500-757, Republic of Korea.

Orally administered tamoxifen undergoes a first-pass metabolism and
substrates for multidrug resistance (MDR) transporters efflux in the
liver and intestines, which obstructs its systemic exposure.
This study investigated the effect of quercetin, a dual inhibitor of
CYP3A4 and P-gp, on the bioavailability and pharmacokinetics of
tamoxifen and one of its metabolites, 4-hydroxytamoxifen, in rats.
The pharmacokinetic parameters of tamoxifen and 4-hydroxytamoxifen in
plasma were determined after orally administering tamoxifen (10 mg/kg)
with or without quercetin (2.5, 7.5 and 15 mg/kg).
The coadministration of quercetin (2.5 and 7.5 mg/kg) significantly (p
< 0.05) increased the absorption rate constant (K(a)), peak
concentration (C(max)) and the areas under the plasma concentration-
time curve (AUC) of tamoxifen.
The absolute bioavailability (AB%) of tamoxifen with 2.5 and 7.5 mg/kg
quercetin ranged from 18.0% to 24.1%, which was significantly higher
than the control group, 15.0% (p < 0.05).
The relative bioavailability (RB%) of tamoxifen coadministered with
quercetin was 1.20-1.61 times higher than the control group. The
coadministration of quercetin caused no significant changes in the
terminal half-life (t(1/2)) and the time to reach the peak
concentration (T(max)) of tamoxifen.
Compared with the control group, the coadministration of 7.5 mg/kg
quercetin significantly (p < 0.05) increased the AUC of 4-
hydroxytamoxifen.
However, the metabolite ratios (MR; AUC of 4-hydroxytamoxifen to
tamoxifen) were significantly lower (p < 0.05).
This suggests that quercetin inhibits the both MDR transporters efflux
and first-pass metabolism of tamoxifen.
The enhanced bioavailability of tamoxifen as a result of its
coadministration with quercetin might be due to the effect of
quercetin promoting the intestinal absorption and reducing the first-
pass metabolism of tamoxifen.
If the results are further confirmed in the clinical trials, the
tamoxifen dosage should be adjusted when tamoxifen is administered
with quercetin or quercetin-containing dietary supplements in order to
avoid potential drug interactions.

PMID: 16516418 [PubMed - indexed for MEDLINE]
----------------

**Therapeutic outcome was coincident with more efficient iron
clearance,
suggesting that one possible mechanism whereby quercetin decreases
secondary
damage is through iron chelation**

J Neurotrauma. 2003 Jun;20(6):583-591.  Related Articles, Links

Quercetin Promotes Functional Recovery Following Acute Spinal Cord
Injury.

Schultke E, Kendall E, Kamencic H, Ghong Z, Griebel RW, Juurlink BH.

Department of Anatomy and Cell Biology, and Department of Surgery,
Division of
Neurosurgery, University of Saskatchewan, Saskatoon, Canada.

We tested the hypothesis that quercetin, a potent Fe(2+)-chelating
flavonoid,
would decrease secondary damage following spinal cord trauma. MRI
studies using
the relaxation of the T1 proton signal caused by Fe(2+) ions and the
dose-dependent reversal of this effect by addition of quercetin in
aqueous
solution were used to guide us to the dosage of quercetin to be used
in animal
experimentations. Forty-four male Wistar rats were used in two
experimental
series to test the hypothesis that administration of quercetin
improves
recovery of motor function after acute traumatic spinal cord injury.
Animals
were subjected to laminectomy and subjected to an extradural 40-g
force clip
compression for 5 sec at T7. Quercetin or saline was administered
intraperitoneally 1 h after injury and then every 12 hr thereafter.
Recovery of
motor function was assessed using BBB scores at weekly intervals for 4
weeks. A
dose of 2.5 micromoles quercetin/kg body weight did not result in
significantly
better functional outcome, whereas doses ranging from 5 to 100
micromoles
quercetin/kg body weight resulted in a significantly better functional
outcome
with half or more of the animals walking, although with deficit; in
contrast,
no animals walked in the group of saline-treated animals. No
significant
differences in behavioral outcome were seen amongst the doses ranging
from 5 to
100 micromol/kg, nor was there a difference if animals were treated
for 4 or 10
days. Therapeutic outcome was coincident with more efficient iron
clearance,
suggesting that one possible mechanism whereby quercetin decreases
secondary
damage is through iron chelation.

PMID: 12906742 [PubMed - as supplied by publisher]

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