To determine the stomach bioreactor capability for food oxidation or antioxidation, rats were fed red turkey meat cutlets (meal A) or red turkey meat cutlets and red wine concentrate (meal B). The hydroperoxides (LOOH) and malondialdehyde (MDA) levels of the stomach contents were evaluated during and after digestion; the postprandial plasma MDA level was also evaluated. In independently fed rats, the stomach LOOH concentration fell substantially 90 min following the meal, and the addition of red wine polyphenols enhanced LOOH reduction 3-fold. A similar trend was obtained for MDA. After pyloric ligation, the stomach contents of rats fed red meat homogenate showed >2-fold increases in LOOH and MDA accumulation. The postprandial plasma MDA level increased significantly by 50% following meal A and was maintained or even fell by 34% below basal level following meal B. The findings show that consumption of partially oxidized food could increase lipid peroxidation in the stomach and the absorption of cytotoxic lipid peroxidation products into the body. The addition of antioxidants such as red wine polyphenols to the meal may alter these outcomes. These findings explain the potentially harmful effects of oxidized fats in foods and the important benefit of consuming dietary polyphenols during the meal.

The Western diet contains large quantities of oxidized lipids, because a large proportion of the food in the diet is consumed in a fried, heated, processed, or stored form. We investigated the reaction that could occur in the acidic pH of the stomach and accelerate the generation of lipid hydroperoxides and cooxidation of dietary vitamins. To estimate the oxygen content in the stomach after food consumption, oxygen released from masticated bread (20 g) into deoxygenated water (100 mL) was measured. Under these conditions, the oxygen concentration rose by 250 microM and reached a full oxygen saturation. The present study demonstrated that heated red meat homogenized in human gastric fluid, at pH 3.0, generated hydroperoxides and malondialdehyde. The cross-reaction between free radicals produced during this reaction cooxidized vitamin E, beta-carotene, and vitamin C. Both lipid peroxidation and cooxidation of vitamin E and beta-carotene were inhibited at pH 3.0 by red wine polyphenols. Ascorbic acid (44 mg) at a concentration that represented the amount that could be ingested during a meal inhibited lipid peroxidation only slightly. Red wine polyphenols failed to prevent ascorbic acid oxidation significantly but, in conjunction with ascorbic acid, did inhibit lipid peroxidation. In the presence of catechin, a well-known polyphenol found in red wine, ascorbic acid at pH 3.0 works in a synergistic manner preventing lipid peroxidation and beta-carotene cooxidation. The present data may explain the major benefits to our health and the crucial role of consuming food products rich in dietary antioxidants such as fruits, vegetables, red wines, or green tea during the meal.

Reactive oxygen species have been postulated to play a role in the pathogenesis of mucosal GI injury and in peptic ulcer disease (PUD). The low molecular weight antioxidants (LMWA) group plays an important role in the defense mechanism of the GI tract against oxidative damage, and is a major component of the reducing capacity of biological tissues and fluids. We hypothesized that altered gastric LMWA anti oxidative status might play a role in the pathogenesis of upper GI disorders such as PUD and could be evaluated by measuring gastric juice reducing power. The aim of the present study was to determine, by cyclic voltammetry, changes in the overall antioxidant activity of the gastric juice in active duodenal ulcer (DU) obtained during upper endoscopy from patients as compared with normal subjects. The results show that in 28/37 (76%) of the control subjects, gastric juice demonstrated a reducing power of at least two anodic waves indicating at least two different LMWA groups. Three or more anodic waves were recorded in 12 normal subject (32%). In contrast, 16/25 (64%) of gastric juice samples obtained from active DU patients exhibited only one anodic wave usually at a high potential (>900 mV). These results imply that gastric juice normally possesses a reducing power profile that can be determined by cyclic voltammetry. This profile is significantly changed in untreated DU disease. These changes in active DU may indicate decreased gastric antioxidant activity reflecting reduced mucosal protection that leading to increased susceptibility of the gastro-duodenum to injury.

A novel assay was developed to measure the capacity of polyphenols to chelate cobalt(II) by using the reduction of the tetrazolium salts, NBT (nitroblue tetrazolium chloride), MTT (methylthiazolyldiphenyl-tetrazolium bromide), and XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) to formazan products. The reduction of the salts is initiated by a cocktail comprised of cobalt(II), H(2)O(2), and selenium(IV), which generates hydroxyl radical, peroxide, and superoxide ions. However, because cobalt(II) could not be replaced either by Fe(II), Mn(II), or Cu(II), the classical Fenton transitional metals, it indicates that cobalt is the key player in the tetrazolium salt reduction. Micromolar concentrations of a large variety of antioxidant polyphenols and minute amounts of fruit beverages rich in polyphenols can readily chelate cobalt, resulting in the inhibition of the reduction of tetrazolium salt to formazan, in a dose-dependent manner. However, this method is unsuitable to measure low molecular weight antioxidants such as ascorbate, uric acid, and vitamin E since these have no chelating properties for cobalt(II). The newly described tetrazolium reduction method is as sensitive as the ferric ion reducing antioxidant power, 2,2-diphenyl-2-picrylhydrazyl hydrate, and the luminol-dependent chemiluminescence antioxidant assays. The practical advantages of using the newly described method to quantify polyphenol levels from various sources are briefly discussed.

Background/Aims: The present study was designed to investigate the short-term safety and efficacy of topical application with body lotion enriched with minerals from the Dead Sea versus 2 different placebo treatments in reducing symptoms of uremic pruritus. Methods: In this single-center, randomized, double placebo-controlled clinical trial, 78 hemodialysis patients with self-reported uremic pruritus were randomized to twice-daily topical treatment with body lotion enriched with minerals from the Dead Sea (DS) or to each of 2 types of placebo:(1) lotion with no Dead Sea minerals but otherwise identical to DS (P1) or (2) lotion with no active ingredients (P2). Symptoms of uremic pruritus (itching, dryness, peeling, tightness) were evaluated at baseline and 2 weeks (14 days) after treatment intervention using a 5-point Likert scale. Results: Following treatment, significant differences in symptom severity scores between DS and P1 and, separately, between group DS and P2, were not detected. Additionally, when DS was compared to the combined placebo groups (P1 and P2 together), significant post-treatment differences in symptom severity scores were not observed. Symptoms were less severe post-treatment regardless of treatment assignment. Conclusions: DS was not superior to either of the placebo treatments in the symptomatic relief of uremic pruritus.

BACKGROUND: Diabetes mellitus is characterized by a chronic hyperglycemia and might cause skin pathologies resulting from an ischemic insult. A variety of mechanisms have been suggested for the damage provided by ischemia-reperfusion injury (IRI) or for hyperglycemic conditions. Yet, the association between IRI and hyperglycemia together in skin has been poorly investigated even thought they are both present in diabetic patients. OBJECTIVE: To examine the effect of a dual stress combining IRI and hyperglycemia on human keratinocytes-its ability to cause oxidative damage and inflammatory response via the enzymes xanthine oxidase (XO) and inducible nitric oxide synthase (iNOS). METHODS: HaCaT cells were used as a model to induce IRI and hyperglycemia. In order to assess the oxidative damage, total antioxidant scavenging capacity (TSC) and GSH/GSSG ratio were evaluated. iNOS expression was evaluated and its metabolite nitric oxide was estimated by measuring nitrite levels. XO activity was assessed by uric acid quantification and by superoxide radical formation. Inflammatory response was determined through interleukin-6 secretion. RESULTS: Our observations demonstrate different responses of the cells exposed to single stress (IRI) compared to dual stress combining also hyperglycemia. However, cells response exhibited similarity during reperfusion, by enhancing iNOS expression as well as superoxide levels. While ischemia led to changes in TSC and redox state, reperfusion restored them to basal levels. IRI also caused the enhancement of secreted IL-6 and uric acid levels. CONCLUSION: iNOS and XO play a major role in IRI and hyperglycemia. Inhibition of one of these enzymes may be beneficial to skin cells under these conditions.

Several microbial species, including probiotic lactic acid bacteria, have the ability to irreversibly bind a large variety of polyphenols (flavonoids) and anthocyanidins found in many colored fruits and vegetables and to enhance their total oxidant-scavenging capacities (TOSC). The binding of flavonoids to microbial surfaces was further increased by the cationic poly electrolytes ligands poly-L-histidine, chlorhexidine and Copaxone(R). This phenomenon was confirmed visually, by the FRAP, DPPH, cyclic voltammetry, Folin-Ciocalteu as well as by luminol-dependent chemiluminescence techniques employed to assay TOSC. The possibility is considered that clinically, microbial cells in the oral cavity and in the gastro intestinal tract, complexed with antioxidant polyphenols from nutrients and with cationic ligands, might increase the protection of mammalian cells against damage induced by excessive generation of reactive oxygen species during infections and inflammation.

Please cite this paper as: Protective effects of a cream containing Dead Sea minerals against UVB-induced stress in human skin. Experimental Dermatology 2009.Abstract Background: Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on psoriasis and other inflammatory skin diseases. Their mode of action, however, remains poorly known. Objectives: To analyse the ability of Dermud, a leave-on skin preparation containing DS mud and other ingredients like DS water, zinc oxide, aloe-vera extract, pro-vitamin B5 and vitamin E, to antagonize biological effects induced by UVB irradiation in skin when topically applied in organ cultures. Methods: We have used human skin organ cultures as a model to assess the biological effects of UVB irradiation and of Dermud cream topical application. Skin pieces were analysed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, for cytokine secretion by solid phase ELISA, for overall antioxidant capacity by ferric reducing antioxidant power and Oxygen radical absorbance capacity assays (epidermis) or by cyclic voltammetry (external medium), and for uric acid (UA) content by HPLC. Results: We report that UVB irradiation decreases cell viability, total antioxidant capacity and UA contents in the epidermis of skin organ cultures, while increasing the levels of apoptosis in cells and their cytokine secretion. Topical application of Dermud decreased all these effects significantly. Conclusions: Our results clearly show that Dermud has protective, anti-oxidant and anti-inflammatory properties that can antagonize biological effects of UVB irradiation in skin. It may therefore be able to reduce skin photodamage and photoaging, and more generally to reduce oxidative stress and inflammation in skin pathologies.

Human umbilical cord blood (HUCB) is a valuable source for cell therapy since it confers neuroprotection in stroke animal models. However, the responsible sub-populations remain to be established and the mechanisms involved are unknown. To explore HUCB neuroprotective properties in a PC12 cell-based ischemic neuronal model, we used an HUCB mononuclear-enriched population of collagen-adherent cells, which can be differentiated in vitro into a neuronal phenotype (HUCBNP). Upon co-culture with insulted-PC12 cells, HUCBNP conferred approximately 30% neuroprotection, as evaluated by decreased lactate dehydrogenase and caspase-3 activities. HUCBNP decreased by 95% the level of free radicals in the insulted-PC12 cells, in correlation with the appearance of antioxidants, as measured by changes in the oxidation-reduction potential of the medium using cyclic-voltammetry. An increased level of nerve growth factor (NGF), vascular endothelial growth factor and basic fibroblast growth factor in the co-culture medium was temporally correlated with a -medium neuroprotection effect, which was partially abolished by heat denaturation. HUCBNP-induced neuroprotection was correlated with changes in gene expression of these neurotrophic factors, while blocked by K252a, an antagonist of the TrkA/NGF receptor. These findings indicate that HUCBNP-induced neuroprotection involves antioxidant(s) and neurotrophic factors, which, by paracrine and/or autocrine interactions between the insulted-PC12 and the HUCBNP cells, conferred neuroprotection.

Increased oxidative stress contributes to the development and progression of both types of diabetes mellitus (DM) and its complications. In the Cohen diabetic (CD) rats, a known genetic model of nutritionally induced type 2 DM, a high-sucrose, low-copper diet (HSD) induces within 4 weeks DM in the sensitive (CDs) rats but not in the resistant (CDr) rats. To assess the possible involvement of oxidative stress in the induction of DM, we studied the effect of HSD on the tissue levels of antioxidants and the extent of oxidative injuries in these animals in comparison with the regular outbred strain of nondiabetic Sabra rats. The specific aims were to investigate, at the onset of HSD-induced DM,(1) the extent of oxidative injury, as reflected by levels of malondialdehyde and protein carbonyl groups;(2) the overall antioxidant capacities to cope with increased oxidative stress; and (3) the modification of oxidative damage biomarkers in various tissues of CDr, CDs, and Sabra rats. Female CDs, CDr, and Sabra rats were fed regular diet or HSD for 4 to 5 weeks; and several parameters of oxidative injuries and antioxidant levels were determined. Changes in the levels of nonenzymatic low-molecular weight antioxidants (LMWAs) were measured by cyclic voltammetry and oxygen radical absorbance capacity. The activities of the antioxidant enzymes superoxide dismutase and catalase were measured. Oxidative damage was evaluated by measuring lipid peroxidation and protein oxidation.(1) In all animals fed HSD, the levels of LMWAs were decreased in most organs, although not plasma.(2) A significant difference was consistently found in antioxidant enzymes' activities in the pancreas of HSD-fed CDs rats, but not in other tissues.(3) The activities of superoxide dismutase and catalase and the levels of malondialdehyde and protein carbonyl group increased, whereas the levels of LMWAs decreased, in the pancreas of HSD-fed CDs rats. In the CD rats that develop DM when fed HSD, the pancreas showed susceptibility to oxidative stress-induced injuries. Thus, enhanced oxidative stress seems to play a role in the pathogenesis of DM in this strain.

Moderate alcohol intake is associated with lower risk of cardiovascular diseases. A large number of epidemiologic studies have demonstrated a U- or J-shaped relation between alcohol consumption and total mortality, coronary heart disease and ischemic stroke. The lowest risk occurs in those who drink one or two drinks per day. Many studies have dealt with the question if specific alcoholic beverage (vodka, beer, wine, liquor) might offer a greater protection. Red wine containing polyphenols is believed to possess exceptional cardioprotective properties, especially if consumed with meals. However, alcohol beverages should not be recommended to patients as a substitute for the well-proven, cardiovascular risk reducing alternatives such as low fat diet, exercise and pharmacotherapy.

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin.

Wine polyphenols are considered to have beneficial effects on CHD and atherosclerosis. The consumption of red wine is high in Italy and France, approximately four times greater than that in the UK. This disparity in red wine consumption is thought to be the reason for the 'French paradox', where France was shown to have a coronary mortality rate close to that of China or Japan despite saturated fat intakes and cholesterol levels similar to the UK and USA. In the present review, we discuss the effects of wine and some of its polyphenol constituents on early pathological indicators of CHD such as plasma lipids, the endothelium and vasculature, platelets and serum antioxidant activity. The review also examines whether the polyphenols or the alcohol in wine is responsible for the effects on markers of heart disease. The present review concludes that red wine polyphenols have little effect on plasma lipid concentrations but wine consumption appears to reduce the susceptibility of LDL to oxidation and increase serum antioxidant capacity. However, these effects do depend on the amount of wine and period of supplementation. Authors who have examined specific polyphenols suggest that some phenolics appear to have endothelium-dependent vaso-relaxing abilities and some a positive effect on NO concentrations. Red wine phenolics also have an inhibitory effect on platelet aggregation, and individual phenolics also have a similar effect in vitro, although it should be noted that there are often discrepancies as large as ten-fold between the concentrations of polyphenolics tested in vitro and their measured levels in vivo. Evidence suggests that alcohol has a positive synergistic effect with wine polyphenols on some atherosclerotic risk factors. Thus evidence that wine drinking is beneficial for cardiac health continues to accumulate but more research is required to understand fully and exactly the functions of red wine polyphenols.

Since now researches claimed that rheumatoid arthritis was not characterized with an inflammatory process due to the lack of vessel in the cartilaginous tissue. Nevertheless, an inflammation of synovial membrane and a reduction of activity of articulation co-exist with rheumatoid arthritis. Recent results have proved that the above disease is connected with an oxidative stress. AIM OF THE STUDY: The aim of this investigation was to estimate changes of nitric oxide (NO) in plasma and malondialdehyd (MDA) concentration in red blood cells of patients suffering from an alloplastic of the hip joint. We also measured how physical activity in a reduced motor activity influences the NO and MDA concentration. MATERIAL AND METHODS: Malonyl dialdehyde (MDA) concentration in RBCs was assayed with Placer method, nitrogen concentration in blood plasma was determined using the Griess indirect method. Biochemical tests have been performed on a group of 36 patients with osteoarthritis hospitalised at the Traumatic-Orthopaedic Department of the Ministry of Internal Affairs and Administration Hospital in Lodz, Poland. A control group included 21 subjects with normal physical activity. RESULTS: The concentration of nitric oxide in plasma of patients that were operated was lower than in a healthy control group. Ten days after the operation it decreased, but after a month it was higher than before the operation. The concentration of MDA in red blood cells was higher before and after the alloplastic than in the healthy control group. Ten days after operation the concentration of MDA was lower about 15.8% but after 30 days it lowered up to about 26.3% in comparison to the concentration before the operation. CONCLUSIONS: Our results are not the same as those shown by other researches which suggest increased production of nitric oxide. Reduction of the motor activity due to degenerative joint disease and alloplastic causes reduction in lipid peroxidation of red blood cells.

Evidence has been provided that red wine possesses antiatherogenic activities in virtue of its content in polyphenols (flavonoids and non-flavonoids substances). Here, some red wines (Negroamaro, Primitivo and Lambrusco) were tested for their ability to trigger nitric oxide (NO) production from human healthy peripheral blood mononuclear cells (PBMC). Negroamaro was the strongest inducer of NO from PBMC and deprivation of polyphenols did not influence its NO generation capacity. This fact supports the involvement of polyphenols in the NO production even in the absence of alcohol, which also per se does not exert any significant activity. These results are also corroborated by the evidence that PBMC inducible-nitric oxide synthase expression occurred by the effect of samples containing polyphenols but this expression was very weak when polyphenols were removed from the whole Negroamaro. In synthesis, flavonoids and resveratrol, major constituents of red wine, once absorbed at intestinal level, enter circulation and trigger monocytes for NO production. To the best of our knowledge, this is the first demonstration of a direct effect of red wine on monocytes for NO release to occur. On the other hand, also the macrophage contingent from gut-associated lymphoid tissue can contribute to NO generation, besides the aliquot produced by endothelial cells, as previously demonstrated by various authors. Taken together, these results support the concept that moderate intake of red wine can prevent atherosclerosis via production of NO, a potent vasodilator of terminal vessels.

Current evidence supports a contribution of polyphenols to the prevention of cardiovascular disease, but their mechanisms of action are not understood. We investigated the impact of red wine polyphenols on postprandial cytotoxic lipid peroxidation products (MDA) levels in humans. In a randomized, crossover study, the effect of red wine polyphenols on postprandial levels of plasma and urine MDA was investigated. Three meals of 250 g turkey cutlets supplemented by water (A); soaked in red wine after heating plus 200 ml of red wine (B); or soaked in red wine prior to heating plus 200 ml of red wine (C) were administered to 10 healthy volunteers. Subject baseline plasma levels of MDA were 50 +/- 20 nM. After a meal of turkey meat cutlets, plasma MDA levels increased by 160 nM (P<0.0001); after (B) there was a 75% reduction in the absorption of MDA (P<0.0001). However, after (C), the elevation of plasma MDA was completely prevented (P<0.0001). Similar results were obtained for MDA accumulation in urine. Our study suggests that red wine polyphenols exert a beneficial effect by the novel new function, absorption inhibition of the lipotoxin MDA. These findings explain the potentially harmful effects of oxidized fats found in foods and the important benefit of dietary polyphenols in the meal.-Gorelik, S., Ligumsky, M., Kohen, R., Kanner, J. A novel function of red wine polyphenols in humans: prevention of absorption of cytotoxic lipid peroxidation products.

AIMS: It has been reported that alcohol has multiple effects on appetite. To elucidate potential mechanisms we measured the levels of plasma leptin and the vasoactive factors after red wine intake. METHODS: We conducted a randomized crossover trial to study the effect of red wine on the levels of leptin, TNF-alpha, TGF- beta(1), IL-6, ICAM-1, and VCAM-1 in healthy, non-smoking individuals. The subjects were randomized to drinking one glass of red wine (150 ml, 15 g alcohol) every day ('wine period') or to undergo a period of total abstention from alcohol ('abstention period'). After 3 weeks they switched the intervention group. Eighty-seven volunteers completed the study (mean age 50 years). RESULTS: After 3 weeks' daily intake of red wine, plasma leptin was significantly increased (from 6308 pg/ml to 7402 pg/ml, P = 0.05). There was a marked gender difference, as leptin levels increased only in females (P = 0.012). When calculated as leptin/body mass index (BMI) ratio, the trend and results were similar. Red wine consumption had no significant effect on other vasoactive factors measured in this study. CONCLUSION: Red wine increases levels of the appetite-regulating hormone leptin in females, but not in males. Whether red wine has an effect on appetite-regulation in its own right, remains to be solved.

BACKGROUND: Red wine consumption is associated with reduced cardiovascular disease mortality. Its cardioprotective properties may be partly related to its ability to improve endothelial function. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of red wine and de-alcoholized red wine improve coronary flow velocity reserve (CFR). METHODS: Using transthoracic Doppler echocardiography, 176 CFR measurements were made in 22 healthy men before and after ingestion of a moderate (4.0+/-0.4dl) and an escalating high dose (total amount 8.1+/-0.9dl) of alcohol-containing red wine and de-alcoholized red wine, which contained similar amounts of phenolic substances. The difference in plasma antioxidant capacity was determined by colorimetric assay kit. RESULTS: Red wine increased CFR from 3.8+/-1.4 to 4.5+/-1.4 (p<0.01) and 4.0+/-1.2 (p=NS) after moderate and high doses, respectively; whereas de-alcoholized red wine had no significant effects on CFR (4.0+/-0.7, 4.3+/-1.3 and 4.5+/-1.4, respectively). Plasma antioxidant capacity increased significantly after high dose of red wine (27.5+/-14.7%, p<0.001), but not after de-alcoholized red wine (0.5+/-10.5%, p=NS) despite similar amounts of phenolic substances. Differences between CFR and plasma antioxidant capacities before and after drinking had no significant association. CONCLUSIONS: A moderate dose of red wine, but not de-alcoholized red wine increases CFR. The increase of CFR is probably mediated by other than direct antioxidant properties of polyphenols, because the simultaneous increase of CFR and plasma antioxidant capacity were not associated.