>Tolcapone and entacapone are the first of a new class of drugs for
>Parkinson's, which inhibit the enzyme,
>catechol-O-methyltransferase (COMT), found in serum and the brain. C=
OMT
>degrades both dopamine and its
>precursor, levodopa, which is the current mainstay of treatment for
>Parkinson's. COMT inhibitors increase brain
>dopamine levels, making them potential adjunct therapies to levodopa=
.
List, I am wondering if taking Quercetin would beneifit some parkin=
son
patients, it looks here that it is also a catechol-o-methyltransferas=
e
inhibitor. Quercetin is a bioflavonoid, primary used for people with=
=20
allergies, sold in all health food stores. I am holding a product fro=
m
GNC in my hand called antioxidant Flavonoid formula, it contains 10 m=
gs
of quercetin powder. I will let you know if it helps my father.
Best Wishes, Linda Forrest's Mom
Title
Quercetin increases the severity of estradiol-induced tumorigene=
sis in
hamster kidney.
Author
Zhu BT; Liehr JG
Address
Department of Pharmacology and Toxicology, University of Texas M=
edical
Branch, Galveston 77555-1031.
Source
Toxicol Appl Pharmacol, 125:149-58, 1994 Mar
Abstract
Catechol estrogens have been postulated to mediate estradiol-ind=
uced
kidney tumorigenesis in Syrian hamsters. As part of an examinati=
on of
this postulate, we studied the influence of quercetin, a polyphe=
nolic
flavonoid, on the incidence and severity of estrogen-induced kid=
ney
tumors, on the metabolic activation of estradiol to catechol est=
rogens,
and on the inactivation of catechol estrogens by
catechol-O-methyltransferase-mediated O-methylation. None of the
hamsters treated with 0.3 or 3% quercetin in the diet for 5.7 or=
6.5
months, respectively, developed tumors, whereas all animals trea=
ted
with estradiol developed kidney tumors. The coadministration of
estradiol plus 3% quercetin significantly (p < 0.05) increased t=
he mean
number of large tumor nodules and the incidence of abdominal met=
astases
over values obtained with hormone treatment alone. The coadminis=
tration
of estradiol plus 0.3 or 3% quercetin for 16 days increased rena=
l
NADPH-dependent estradiol-4- but not estradiol-2-hydroxylase act=
ivities
by 91 or 73%, respectively, over values obtained with hormone tr=
eatment
alone.
In vitro, quercetin and its structural analog, fisetin, strongly
inhibited the catechol-O-methyltransferase-catalyzed O-methylati=
on of
60 microM 4-hydroxyestradiol, with IC50 values of approximately =
2-4
microM.
Kinetic analyses of the enzyme inhibition by quercetin and
fisetin revealed a mixed-type of inhibition (competitive plus
non-competitive). Combined treatment of estradiol plus 3% querce=
tin
decreased the rates of kidney catechol-O-methyltransferase-catal=
yzed
O-methylation of 2- and 4-hydroxyestradiol by 34 and 22%, respec=
tively,
from values obtained with hormone treatment alone. Rates of hams=
ter
liver and kidney microsome-mediated estrogen quinone formation a=
nd
quinone reduction (redox cycling) in estradiol plus 3%
quercetin-treated hamsters were not markedly altered compared to=
values
obtained in estradiol-treated animals. It is concluded that incr=
eased
rates of formation of 4-hydroxyestradiol combined with an inhibi=
tion of
the inactivation of this catechol estrogen by
catechol-O-methyltransferase may result in elevated levels of th=
is
estrogen metabolite, specifically in the hamster kidney, where i=
t may
undergo metabolic redox cycling and generate potentially mutagen=
ic free
radicals. Thus, the potentiation by quercetin of estradiol-induc=
ed
tumorigenesis in hamster kidney supports a role of 4-hydroxyestr=
adiol
in estrogen-induced carcinogenesis in this species.
Language
Eng
Unique Identifier
94174573
---------------------------------------------------------------------=
-------
MESH Headings
Animal; Biotransformation*; Catechol Methyltransferase*; Cytochr=
ome
P-450*; Drug Synergism*; Estradiol*; Estrogens, Catechol*; Flavo=
nes*;
Hamsters*; Kidney*; Kidney Neoplasms*; Male; Mesocricetus*;
Methylation*; Microsomes, Liver*; NADP*; Oxidation-Reduction*;
Quercetin*; Steroid Hydroxylases*; Support, U.S. Gov't, P.H.S.
---------------------------------------------------------------------=
-------
Publication Type
JOURNAL ARTICLE
ISSN
0041-008X
Country of Publication
UNITED STATES
---------------------------------------------------------------------=
-------
http://www.medscape.com
Medscape is produced by Medscape, Inc.
All material on this server Copyright =A9 1994, 1995, 1996, 1997 =
by the
publishers involved.
[Click this icon to load the navigation map (0.9Kb)]
