X-Message-Number: 32184
Date: Sun, 29 Nov 2009 10:47:49 -0800 (PST)
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Subject: cryoprotectant toxicity neutralization by quercetin II
Transplantation. 2005 Dec 15;80(11):1556-9.
Beneficial effects of the bioflavonoids curcumin and quercetin on early function
in cadaveric renal transplantation: a randomized placebo controlled trial.
Shoskes D, Lapierre C, Cruz-Correa M, Muruve N, Rosario R, Fromkin B, Braun M,
Copley J. Department of Kidney Transplantation, Cleveland Clinic Florida,
Weston, FL, USA. Erratum in: Transplantation. 2006 Sep 15;82(5):715.
Cruz-Corerra, Marcia [corrected to Cruz-Correa, Marcia].
BACKGROUND: The bioflavonoids quercetin and curcumin are renoprotective
natural antioxidants. We wished to examine their effects on early graft
function (EF). METHODS: Between September 2002 and August 2004, 43 dialysis
dependent cadaveric kidney recipients were enrolled into a study using Oxy-Q
which contains 480 mg of curcumin and 20 mg of quercetin, started after
surgery and taken for 1 month. They were randomized into three groups:
control (placebo), low dose (one capsule, one placebo) and high dose (two
capsules). Delayed graft function (DGF) was defined as first week dialysis
need and slow function (SGF) as Cr >2.5 mg/dl by day 10. Category variables
were compared by chi squared and continuous variables by Kruskal-Wallis.
RESULTS: There were four withdrawals: one by patient choice and three for
urine leak. The control group had 2/14 patients with DGF vs. none in either
treatment group. Incidence of EF was control 43%, low dose 71% and high dose
93% (P=0.013). Serum creatinine was significantly lower at 2 days (control
7.6+/-2.1, low 5.4+/-0.6, high 3.96+/-.35 P=0.0001) and 30 days (control
1.82+/-.16, low 1.65+/-.09, high 1.33 +/-.1, P=0.03). Acute rejection
incidence within 6 months was control 14.3%, low dose 14.3% and high dose
0%. Tremor was detected in 13% of high dose patients vs. 46% of others.
Urinary HO-1 was higher in bioflavonoid groups. CONCLUSION: Bioflavonoid
therapy improved early graft function. Acute rejection and neurotoxicity
were lowest in the high dose group. These bioflavonoids improve early
outcomes in cadaveric renal transplantation, possibly through HO-1
induction.
PMID: 16371925
Transplant Proc. 2001 Sep;33(6):2988.
Quercetin and curcumin up-regulate antioxidant gene expression in rat kidney
after ureteral obstruction or ischemia/reperfusion injury.
Shahed AR, Jones E, Shoskes D. Harbor-UCLA Medical Center, Torrance, California,
USA.
PMID: 11543823
Transplantation. 2006 Jan 27;81(2):231-9.
Improved cold preservation of kidney tubular cells by means of adding
bioflavonoids to organ preservation solutions.
Ahlenstiel T, Burkhardt G, Kohler H, Kuhlmann MK. Department of Medicine,
Division of Nephrology and Hypertension, University Hospital of Saarland,
Homburg/Saar, Germany.
BACKGROUND: Cold ischemia and reperfusion during renal transplantation
result in release of reactive oxygen species. The aim of this study is to
examine whether cold storage induced cell injury can be ameliorated by
adding flavonoids directly to preservation solutions. METHODS: Cultured
renal tubular epithelial cells (LLC-PK1) were stored in University of
Wisconsin (UW) or Euro-Collins (EC) solution at 4 degrees C for 20 hours.
Preservation solutions were supplemented with various flavonoids. After
rewarming, structural and metabolic cell integrity was measured by lactate
dehydrogenase (LDH) release and MTT-test, and lipid peroxidation was
assessed from generation of thiobarbituric acid-reactive substances (TBARS).
RESULTS: Twenty hours of cold storage resulted in a substantial loss of
cell viability in both preservation solutions (in EC: LDH release
92.4+/-2.7%; MTT-test 0.5+/-0.7%). Addition of luteolin, quercetin,
kempferol, fisetin, myricetin, morin, catechin, and silibinin significantly
reduced cell injury (for luteolin in EC: LDH release 2.4+/-1.6%; MTT-test
110.3+/-10.4%, P<0.01; TBARS-production (related to cold stored control
cells) 8.9+/-2.6%). No cytoprotection was found for apigenin, naringenin,
and rutin. Protective potency of flavonoids depends on number of
hydroxyl-substituents and lipophilicity of the diphenylpyran compounds.
CONCLUSION: Cold storage induced injury of renal tubular cells was
substantially ameliorated by adding selected flavonoids directly to
preservation solutions.
PMID: 16436967
Kidney Int. 2003 Feb;63(2):554-63.
Bioflavonoids attenuate renal proximal tubular cell injury during cold
preservation in Euro-Collins and University of Wisconsin solutions.
Ahlenstiel T, Burkhardt G, Kohler H, Kuhlmann MK. Department of Medicine,
Division of Nephrology and Hypertension, University Hospital of Saarland,
Homburg/Saar, Germany.
BACKGROUND: Cold ischemia and reperfusion during kidney transplantation are
associated with release of free oxygen radicals and damage of renal tubular
cells. Bioflavonoids may diminish cold storage-induced injury due to
antioxidant and iron chelating activities. This study was designed to
delineate the renoprotective mechanisms of bioflavonoids and to define the
structural features conferring cytoprotection from cold injury. METHODS:
LLC-PK1 cells were preincubated for three hours with bioflavonoids and cold
stored in University of Wisconsin (UW)- or Euro-Collins (EC)-solution for 20
hours. After rewarming, cell viability was assessed by the lactate
dehydrogenase (LDH) release, MTT-test, and amino acid transport activity.
Lipid peroxidation was assessed from the generation of thiobarbituric
acid-reactive substances. RESULTS: Twenty-hours of cold storage of LLC-PK1
cells resulted in a substantial loss of cell integrity that was more
pronounced in the EC (LDH release, 93.6 +/- 1.6%) than the UW solution (67.2
+/- 6.9%; P < 0.0001). Pretreatment with quercetin significantly enhanced
cell survival (LDH release, 5.4 +/- 2.7% for UW and 8.4 +/- 4.2% for EC) in
a concentration dependent manner. Structure-activity studies revealed
similar renoprotection for kaempferol, luteolin and fisetin, unlike
myricetin, morin, apigenin, naringenin, catechin, silibinin and rutin. Lipid
peroxidation was reduced (UW alone, 2.7 +/- 1.2 vs. UW+quercetin 0.5 +/-
0.2 nmol/mg protein, P < 0.01), and l-threonine uptake completely sustained
by pretreatment with quercetin, kaempferol, luteolin, and fisetin. However,
renoprotection by fisetin was rapidly lost during rewarming. Protective
properties of bioflavonoids were governed by the number and arrangement of
hydroxyl substitutes, electron-delocalization, sterical planarity, and
lipophilicity of the basic diphenylpyran skeleton. CONCLUSION: Cold
storage-induced renal tubular cell injury is ameliorated by bioflavonoids.
Renoprotective effects of bioflavonoids are defined by structure, suggesting
that flavonoids are incorporated into membrane lipid bilayers and interfere
with membrane lipid peroxidation.
PMID: 12631120
Skin Pharmacol Physiol. 2009 Sep 25;22(6):299-304. [Epub ahead of print]
Skin Penetration of Epigallocatechin-3-Gallate and Quercetin from Green Tea and
Ginkgo biloba Extracts Vehiculated in Cosmetic Formulations.
Dal Belo SE, Gaspar LR, Maia Campos PM, Marty JP. Faculdade de Ciencias
Farmaceuticas de Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
Green tea (Camellia sinensis) and Ginkgo biloba extracts in cosmetic
formulations have been suggested to protect the skin against UV-induced
damage and skin ageing. Thus, it is very important to assess the human skin
penetration of their major flavonoids to verify if they penetrate and remain
in the skin to exert their proposed effects. The aim of this study was to
evaluate the human skin penetration of epigallocatechin-3-gallate (EGCG) and
quercetin from green tea and G. biloba extracts vehiculated in cosmetic
formulations. This study was conducted with fresh dermatomed human Caucasian
skin from abdominal surgery mounted on static Franz diffusion cells. Skin
samples were mounted between two diffusion half-cells and 10 mg/cm(2) of
formulations supplemented with 6% of green tea or G. biloba extract were
applied on the skin surface. The receptor fluid was removed after 6 and 24 h
and analyzed by high-performance liquid chromatography for the
quantification of the flavonoids. The stratum corneum was removed by tape
stripping and immersed in methanol and the epidermis was mechanically
separated from the dermis and triturated in methanol to extract EGCG and
quercetin. The results showed that the flavonoids under study penetrated
into the skin, without reaching the receptor fluid. The majority of EGCG was
quantified in the stratum corneum (0.87 mug/cm(2)), which was statistically
higher than the EGCG concentrations found in viable epidermis (0.54
mug/cm(2)) and in the dermis (0.38 mug/cm(2)). The majority of quercetin was
quantified in the viable epidermis (0.23 mug/cm(2)), which was
statistically higher than the EGCG concentration found in the stratum
corneum layer (0.17 mug/cm(2)). Finally, it can be concluded that EGCG and
quercetin from green tea and G. biloba extracts vehiculated in cosmetic
formulations presented good skin penetration and retention, which can favor
their skin effects. Copyright C 2009 S. Karger AG, Basel.
PMID: 19786823
Nanomedicine. 2008 Mar;4(1):70-8. Epub 2008 Jan 30.
Anxiety and cognitive effects of quercetin liposomes in rats.
Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S.
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Quercetin, an effective flavonol used as an antioxidant, was investigated
for its anxiolytic and cognitive activities in male Wistar rats. Oral
quercetin (300 mg/kg body weight/day) was compared with oral and intranasal
quercetin liposomes (20 microg/day). Quercetin liposomes, in a mixture of
egg phosphatidylcholine, cholesterol, and quercetin (2:1:1) and dispersed in
50% polyethylene glycol in water, were approximately 200 nm in mean
particle diameter and negative surface charge with a range of encapsulation
efficiency of 60% to 80%. Anxiolytic and cognitive-enhancing effects of
quercetin, conventional and liposomal, were subjected to elevated plus maze
and Morris water maze tests, respectively. Both conventional and quercetin
liposomes showed anxiolytic and cognitive-enhancing effects. A lower dose
and a faster rate were observed with intranasal quercetin liposomes when
compared with oral quercetin, conventional and liposomal. The intranasal
quercetin liposomes are effective in the delivery of quercetin to the
central nervous system.
PMID: 18249157
Clin Cancer Res. 2006 May 15;12(10):3193-9.
Liposomal quercetin efficiently suppresses growth of solid tumors in murine
models.
Yuan ZP, Chen LJ, Fan LY, Tang MH, Yang GL, Yang HS, Du XB, Wang GQ, Yao WX,
Zhao QM, Ye B, Wang R, Diao P, Zhang W, Wu HB, Zhao X, Wei YQ. State Key
Laboratory of Biotherapy, West China Hospital, West China Medical School,
Sichuan University, Chengdu, Sichuan, People's Republic of China.
PURPOSE: Quercetin is a potent chemotherapeutic drug. Clinical trials
exploring different schedules of administration of quercetin have been
hampered by its extreme water insolubility. To overcome this limitation,
this study is aimed to develop liposomal quercetin and investigate its
distribution in vivo and antitumor efficacy in vivo and in vitro.
EXPERIMENTAL DESIGN: Quercetin was encapsulated in polyethylene glycol 4000
liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg in
tumor-bearing mice was detected by high-performance liquid chromatography.
Induction of apoptosis by liposomal quercetin in vitro was tested. The
antitumor activity of liposomal quercetin was evaluated in the
immunocompetent C57BL/6N mice bearing LL/2 Lewis lung cancer and in BALB/c
mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and
survival time were observed. The mechanisms underlying the antitumor effect
of quercetin in vivo was investigated by detecting the microvessel density,
apoptosis, and heat shock protein 70 expression in tumor tissues. RESULTS:
Liposomal quercetin could be dissolved in i.v. injection and effectively
accumulate in tumor tissues. The half-time of liposomal quercetin was 2
hours in plasma. The liposomal quercetin induced apoptosis in vitro and
significantly inhibited tumor growth in vivo in a dose-dependent manner. The
optimal dose of liposomal quercetin resulted in a 40-day survival rate of
40%. Quantitative real-time PCR showed that liposomal quercetin
down-regulated the expression of heat shock protein 70 in tumor tissues.
Immunohistochemistry analysis showed that liposomal quercetin inhibited
tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis.
CONCLUSIONS: Our data indicated that pegylated liposomal quercetin can
significantly improve the solubility and bioavailability of quercetin and
can be a potential application in the treatment of tumor.
PMID: 16707620
[Quercetin -mediated cytoprotection is apparently maintained indefinitely in
frozen cells.]
Mutagenesis. 2002 May;17(3):211-4.
Cryopreserved versus freshly isolated lymphocytes in human biomonitoring:
endogenous and induced DNA damage, antioxidant status and repair capability.
Duthie SJ, Pirie L, Jenkinson AM, Narayanan S. Rowett Research Institute,
Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK.
Lymphocytes are routinely used in human biomonitoring to assess the
potential toxic and cytoprotective effects of diet on both DNA damage and
repair and, by implication, health. Logistically, samples may require to be
cryopreserved and stored. How this affects cells used in human biomonitoring
is often not considered. In this study we have evaluated the influence of
cryopreservation on endogenous and induced DNA strand breakage, altered
bases (oxidized purines, oxidized pyrimidines and misincorporated uracil),
antioxidant capacity and DNA repair capability in human peripheral blood
lymphocytes. Neither isolation nor freezing increased DNA strand breakage
above endogenous levels found in freshly isolated human lymphocytes.
Oxidized bases (both pyrimidines and purines) and misincorporated uracil,
were similar for fresh and frozen lymphocytes. Fresh and frozen lymphocytes
responded almost identically to hydrogen peroxide. Quercetin-mediated
cytoprotection against hydrogen peroxide-induced strand breakage was
maintained in cryopreserved lymphocytes after short-term (24 h) and longer
term (2 months) storage compared with freshly isolated and treated cells.
Hydrogen peroxide-induced DNA strand breakage was repaired in fresh
lymphocytes. Cryopreserved lymphocytes were unable to repair oxidant-induced
DNA strand breaks. Frozen human lymphocytes can therefore be successfully
used for most aspects of DNA damage biomonitoring, but not for repair.
PMID: 11971991
Plant Cell Environ. 2008 Sep;31(9):1335-48. Epub 2008 Jun 3.
Deep supercooling xylem parenchyma cells of katsura tree (Cercidiphyllum
japonicum) contain flavonol glycosides exhibiting high anti-ice nucleation
activity.
Kasuga J, Hashidoko Y, Nishioka A, Yoshiba M, Arakawa K, Fujikawa S. Research
Faculty and Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.
Xylem parenchyma cells (XPCs) of boreal hardwood species adapt to
sub-freezing temperatures by deep supercooling to maintain a liquid state of
intracellular water near -40 degrees C. Our previous study found that crude
xylem extracts from such tree species exhibited anti-ice nucleation
activity to promote supercooling of water. In the present study, thus, we
attempted to identify the causative substances of supercooling. Crude xylem
extracts from katsura tree (Cercidiphyllum japonicum), of which XPCs
exhibited deep supercooling to -40 degrees C, were prepared by methanol
extraction. The crude extracts were purified by liquid-liquid extraction and
then by silica gel column chromatography. Although all the fractions
obtained after each purification step exhibited some levels of anti-ice
nucleation activity, only the most active fraction was retained to proceed
to the subsequent level of purification. High-performance liquid
chromatography (HPLC) analysis of a fraction with the highest level of
activity revealed four peaks with high levels of anti-ice nucleation
activity in the range of 2.8-9.0 degrees C. Ultraviolet (UV), mass and
nuclear magnetic resonance (NMR) spectra revealed that these four peaks
corresponded to quercetin-3-O-beta-glucoside (Q3G),
kaempferol-7-O-beta-glucoside (K7G), 8-methoxykaempferol-3-O-beta-glucoside
(8MK3G) and kaempferol-3-O-beta-glucoside (K3G). Microscopic observations
confirmed the presence of flavonoids in cytoplasms of XPCs. These results
suggest that diverse kinds of anti-ice nucleation substances, including
flavonol glycosides, may have important roles in deep supercooling of XPCs.
PMID: 18518920
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