Clin Transl Oncol.
2005 Apr;7(3):115-21.
[Experimental model for treating pulmonary metastatic melanoma
using grape-seed extract, red wine and ethanol.]
[Article in Spanish]
Martinez Conesa C, Vicente Ortega V, Yanez Gascon MJ, Garcia Reverte JM,
Canteras Jordana M, Alcaraz Banos M.
Catedra de Anatomia Patologica. Facultad de Medicina. Universidad
de Murcia. Murcia. Espana.
INTRODUCTION. Melanoma is one of the neoplasias that most frequently
metastasize, especially in the lung, where represents a challenge in oncology
since current treatment is ineffective, and mortality is high. MATERIAL
AND METHODS. Swiss mice (n = 52) were inoculated with 0.5 x 106 B16F10
cell lines and, later, given an oral administration of grape-seed extract,
red wine or ethanol. Metastatic nodules on the lung surface were counted
and, after processing for microscopy, five sections were selected for
image analysis and the invasion index was calculated. RESULTS. Macroscopic
analysis showed that grape-seed extract and red wine reduced the number
of metastatic nodules by 26.07 and 20.81%, respectively, compared with
a control group treated with ethanol. Microscopically, the reduction in
the invasion index was 31.65 for grape-seed extract and 17.57% for red
wine. CONCLUSION. Ethanol administration significantly increased pulmonary
metastasis while grape-seed extract and red wine led to their reduction.
Alcohol Clin Exp Res. 2005 Apr;29(4):664-71.
Effect of red wine on the intestinal absorption of thiamine and
folate in the rat: comparison with the effect of ethanol alone.
Lemos C, Azevedo I, Martel F.
Department of Biochemistry (U38-FCT), Faculty of Medicine, University
of Porto, Porto, Portugal.
BACKGROUND: This work aimed to investigate, in the rat, the acute in
vitro effect of red wine and the effect of chronic red wine ingestion
on the intestinal absorption of thiamine and folate and to compare them
with the effects of ethanol alone. METHODS: The effects of red wine and
of an ethanol solution (same ethanol concentration as that in the red
wine, i.e., 12% [v/v]) on rat jejunal apparent permeability (Papp) to
H-thiamine and H-folate in the mucosal-to-serosal direction were investigated.
Red wine and ethanol were tested both chronically (21-day consumption)
and acutely in vitro. RESULTS: Acutely, both red wine and ethanol 12%
(v/v) (both diluted 1:5) reduced (to 65 and 60% of control, respectively)
the mucosal-to-serosal Papp to H-thiamine across rat jejunum. Chronic
(21-day) ethanol (12% [v/v]) consumption also decreased the Papp to H-thiamine
(to 33% of control), but red wine consumption for the same period did
not change it. Mucosal-to-serosal Papp to H-folate across rat jejunum
was not changed by chronic ingestion of red wine or ethanol. Similarly,
it was not affected by acute exposition of the tissue to red wine or ethanol.
Acute ethanol (0.05% [v/v]) did not affect the Papp to H-thiamine or H-folate
in jejunal tissues obtained from control and red wine-treated rats, but
it significantly increased the Papp to both H-thiamine and H-folate (to
183 and 197% of control, respectively) in tissues from chronically ethanol-treated
rats. CONCLUSIONS: Acute and chronic red wine or ethanol had no effect
on the intestinal absorption of folate. However, ethanol, both acutely
and chronically, decreased the jejunal absorption of thiamine, and red
wine reduced the jejunal absorption of thiamine, but only when tested
acutely. These findings show that it is not correct to extrapolate from
results obtained with ethanol alone on intestinal permeability to the
effect of alcoholic beverage consumption.
Tohoku J Exp Med. 2005 Jun;206(2):141-50.
Suppressive effects of red wine polyphenols on voltage-gated ion
channels in dorsal root ganglionic neuronal cells.
Wu YL, Ohsaga A, Oshiro T, Iinuma K, Kondo Y, Ebihara S, Sasaki
H, Maruyama Y.
Department of Physiology, Tohoku University Graduate School of Medicine,
Sendai 980-8575, Japan.
Polyphenols are ubiquitous plant metabolites with multiple pharmacological
properties. Using whole-cell patch-clamp current recording techniques,
we studied the effects of polypnenols extracted from red wine (purity
> 90% from Cabernet Sauvignon grape wine) on the activities of voltage-operated
Na+-, K+-, and Ca2+-channel currents in mouse dorsal root ganglionic neuronal
cells. The polyphenols suppressed all of the channel activities with half-effective
concentrations of about 2.5, 4.0, and 0.8-1.5 micro g/ml, respectively.
In contrast, they showed no noticeable effects on the ion channels in
other types of cells, including large conductance K+-channels in mouse
lacrimal acinar cells. Thus, the polyphenols suppress firings of the action
potential in the neuronal cells and could show a sedative effect on the
excitation. We expect that red wine can be used as a remedy for excessive
sensory stimuli.
J Agric Food Chem. 2005 May 18;53(10):4220-7.
Redox chemistry of red wine. Quantification by an oscillating
reaction of the overall antioxidant power as a function of the temperature.
Prenesti E, Toso S, Berto S.
Dipartimento di Chimica Analitica dell'Universita, Via Pietro Giuria
5, I-10125, Torino, Italy.
The redox and acid-base reactivity of red wines was studied from both
the analytical and kinetic standpoint. Four homemade wines, made from
Italian red grape varieties of two different vintages, were tested to
study the effect of temperature (25 and 37 degrees C) on the overall antioxidant
power, through the Briggs-Rauscher oscillating reaction. The reaction
was monitored by potentiometry (platinum electrode) and by direct chronometric
detection. A reference scale based on the response of gallic acid was
also employed, so as to achieve a quantitative evaluation: the novel Briggs-Rauscher
antioxidant index (BRAI) was developed to express the overall antioxidant
power quantitatively versus the chosen standard molecule. Overall antioxidant
power was found to be related to total polyphenol content measured using
the Folin-Ciocalteu method: the older wines had a lower antioxidant ability.
Total acidity was also estimated indirectly by means of coupled pH-metric/photometric
titrations and visible spectrophotometric measurements; it revealed an
overlap between acid-base and redox chemistry of red wine.
Sci Aging Knowledge Environ. 2004 Jul 14;2004(28):NF67
Resveratrol to the rescue
Leslie M.
A yeast is a worm is a fly is a person? At least the first three creatures
live longer when they sup an extract of red wine, according to new research.
The chemical activates related enzymes in all three organisms and might
duplicate the effects of extreme dieting. By showing for the first time
that the compound works in animals, the results bring human studies a
step closer.
Int J Vitam Nutr Res. 2004 Mar;74(2):137-43
Red wine consumption prevents vascular oxidative stress
induced by a high-fat meal in healthy volunteers
Ventura P, Bini A, Panini R, Marri L, Tomasi A, Salvioli
G
Dept. of Internal Medicine, Section of Geriatrics and Gerontology, University
of Modena and Reggio Emilia, Italy
In order to investigate the effect of red wine on plasma lipid and oxidative
stress parameters after a high-fat meal, fifteen healthy volunteers were
studied: three days after a high-fat meal with 250 mL of water, they received
the same meal with 250 mL of red wine. During both periods, serial blood
samples were drawn before and 2, 4, and 8 hours after the meal to evaluate
plasma lipids (cholesterol and triglycerides; retinyl palmitate), oxidative
stress (D-ROM, and malondialdehyde) and antioxidant (total plasma antioxidant
levels and uric acid) parameters. During the meal without wine, plasma
lipid parameters increased significantly, whereas plasma total plasma
antioxidant levels decreased, and a trend toward reduction of uric acid
levels was seen). A similar trend in lipid parameters was observed after
the meal with wine; no significant difference in individual lipid parameter
trends after a meal with and without wine was observed. Wine ingestion
induced higher total plasma antioxidant levels and uric acid; malondialdehyde
levels remained constant after wine ingestion. Plasma D-ROM showed a significant
postprandial increase in both experiments, but it was significantly lowered
after wine ingestion. Our results give evidence of oxidative stress following
a fat-rich meal in healthy subjects, suggesting that ingestion of red
wine during a high-fat meal significantly reduces oxidative stress without
inducing any significant modification in postprandial lipemia.
J Vasc Surg. 2004 Jul;40(1):138-45
Resveratrol, a red wine polyphenol, protects spinal
cord from ischemia-reperfusion injury
Kiziltepe U, Turan NN, Han U, Ulus AT, Akar F
Department of Cardiovascular Surgery, S.B. Dr. Muhittin Ulker Emergency
and Traumatology Hospital, Ankara, Turkey
OBJECTIVE: The cardioprotective effect of red wine has been attributed
to resveratrol. The resveratrol-induced protection against ischemia-reperfusion
(I/R) injury has been documented in heart, kidney, and brain. Resveratrol
scavenges free O(2) radicals and upregulates nitric oxide (NO). However,
the presence of resveratrol-induced spinal cord protection against I/R
injury has not been reported in the literature. The objective of this
study was to evaluate the effects of resveratrol on neurologic functions,
histopathologic changes, and NO metabolism following temporary spinal
cord ischemia (SCI) in rabbits.Material and methods SCI was induced with
occlusion of the infrarenal aorta in rabbits. In addition to the sham
group (group S, n = 7), group C (n = 7) received vehicle 30 minutes before
ischemia. Group R1 (n = 7) and R10 (n = 7) received 1 mg/kg and 10 mg/kg
resveratrol instead of vehicle, respectively. Blood samples were taken
to obtain nitrite/nitrate levels during the surgical procedure. After
neurologic evaluation at the 48th hour of reperfusion, lumbar spinal cords
were removed for histopathologic examination and malondialdehyde measurement
as a marker of oxidative stress. RESULTS: Five animals in group C had
paraplegia while 5 in group R10 had normal neurologic functions. The average
Tarlov score of group R10 was significantly higher than that the score
of group C (4.1 +/- 1.2, vs 1.2 +/- 2.2; P =.014). Histopathologic examination
revealed higher neuronal viability index in group R10 compared with that
of group C (0.82 +/- 0.24 vs. 0.46 +/- 0.34; P =.018). Nitrite/nitrate
levels decreased in group C (from 357 +/- 20.15 micromol/L to 281 +/-
47.9 micromol/L; P <.01) whereas they increased both in group R1 and
group R10 (from 287+/-28 micromol/L to 310 +/- 33.9 micromol/L and from
296 +/- 106 micromol/L to 339 +/- 87 micromol/L, respectively) during
SCI. Malondialdehyde levels of group R10 was lower than those of group
C (55 +/- 12.9 nmol/mg protein vs 83.9 +/- 15.1 nmol/mg protein; P =.001,
respectively). CONCLUSIONS: In this model of SCI, resveratrol decreased
oxidative stress, increased NO release, and protected spinal cord from
I/R injury. Resveratrol-induced neuroprotection is probably mediated by
its antioxidant and NO promoting properties. Before considering the clinical
use of this natural antioxidant, further research is warranted about its
mechanism of effects, timing, and optimum dose. CLINICAL RELEVANCE: Paraplegia
that results from spinal cord ischemia is a catastrophic complication
of thoracic and thoracoabdominal aorta surgical procedures. Despite several
surgical modifications and pharmacologic approaches, paraplegia has not
been totally eliminated. On clinical grounds, the efficiency of currently
used pharmacologic agents to prevent spinal cord injury during thoracic
and thoracoabdominal aorta surgery is very limited and their benefit is
controversial. Preischemic infusion of resveratrol protects the spinal
cord from ischemia reperfusion injury in rabbits. Following clarification
of the underlying protective mechanism, optimal dose, and timing, resveratrol
may used in humans as an adjunct to eliminate this catastrophic complication.
Carcinogenesis. 2004 Jun 24
Resveratrol induces FasL-related apoptosis through
Cdc42 activation of ASK1/JNK-dependent signaling pathway in human leukemia
HL-60 cells
Su JL, Lin MT, Hong CC, Chang CC, Shiah SG, Wu CW, Chen
ST, Chau YP, Kuo ML
Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology,
College of Medicine, National Taiwan University, Taipei, Taiwan
Trans-resveratrol, a phytoalexin found at high levels in grapes and in
grape products such as red wine, has been shown to prevent carcinogenesis
or anti-tumor growth in murine models. Here we dissect the detailed signaling
pathway involved in resveratrol-induced apoptosis. Our data showed that
treatment with resveratrol induced activation of apoptosis signal-regulating
kinase 1, a mitogen-activated protein kinase kinase kinase, in turn, activated
the downstream kinases c-Jun N-terminal kinase and p38 mitogen-activated
protein kinase, but not extracellular signal-regulated kinase. Transfection
with a dominant-negative c-Jun Nterminal kinase expression vector reduced
FasL expression and DNA fragmentation induced by resveratrol. However,
inhibition of p38 mitogen-activated protein kinase activity bytreatment
with SB203580 (p38 mitogen-activated protein kinase specific inhibitor)
or expression of mutant p38 mitogen-activated protein kinase expression
vector did not alter the apoptosis and FasL expression in response to
resveratrol. Furthermore, genetic inhibition of apoptosis signal-regulating
kinase 1 signaling inhibited not only the activation of c-Jun N-terminal
kinase, but also the expression of FasL and apoptosis. Similarly, over-expression
of wild type apoptosis signal-regulating kinase 1 strengthened the resveratrol-induced
c-Jun Nterminal kinase activation, FasL expression and subsequent apoptosis.
These results suggest the possible involvement of apoptosis signal-regulating
kinase 1/c-Jun N-terminal kinase signaling in the regulation of FasL expression
and subsequent apoptosis induced by resveratrol in HL-60 cells. Resveratrol
also activated the small GTP-binding protein Cdc42, rather than other
members such as RhoA or Rac1. Expression of a mutant Cdc42 (N17 Cdc42)
dramatically reduced resveratrol-induced JNK activity, FasL expression
and apoptotic cell death. These results showed that resveratrol induced
apoptosis through the Cdc42/ apoptosis signal-regulating kinase 1/c-Jun
N-terminal kinase/FasL signaling cascade in HL-60 cells.
