Red wine-dependent reduction of nitrite to nitric oxide in the stomach (original) (raw)
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Current Drug Targets, 2011
Until recently, nitrite has been considered a stable and inert metabolite of nitric oxide ( • NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to • NO and thus one may consider a reversible interaction regarding • NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest • NO reservoir in the body. This notion has obvious importance when considering that • NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages-containing polyphenols, a rich chemistry occurs in which • NO, • NO-derived species and nitroso or nitrated derivatives may be formed. Most of these molecules may play an important role in vivo. For instance, it has been shown that polyphenol-catalyzed nitrite reduction to • NO may induce local vasodilation and that ethanol (from wine) reacts with • NO-derived species yielding nitroso derivatives endowed with • NO-donating properties. Thus, this review reveals new pathways for the biological effects of dietary nitrite encompassing its interaction with dietary components (polyphenols, red wine, lipids), yielding products with impact on human physiology and pathology, namely cardiovascular, urinary and gastrointestinal systems. Novel therapeutic strategies are therefore expected to follow the elucidation of the mechanisms of nitrite biology.
Toxicology, 2009
Until recently, nitrite has been considered a stable and inert metabolite of nitric oxide ( • NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to • NO and thus one may consider a reversible interaction regarding • NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest • NO reservoir in the body. This notion has obvious importance when considering that • NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages-containing polyphenols, a rich chemistry occurs in which • NO, • NO-derived species and nitroso or nitrated derivatives may be formed. Most of these molecules may play an important role in vivo. For instance, it has been shown that polyphenol-catalyzed nitrite reduction to • NO may induce local vasodilation and that ethanol (from wine) reacts with • NO-derived species yielding nitroso derivatives endowed with • NO-donating properties. Thus, this review reveals new pathways for the biological effects of dietary nitrite encompassing its interaction with dietary components (polyphenols, red wine, lipids), yielding products with impact on human physiology and pathology, namely cardiovascular, urinary and gastrointestinal systems. Novel therapeutic strategies are therefore expected to follow the elucidation of the mechanisms of nitrite biology.
Life Sciences, 2005
Due to the increasing importance of nitrosative stress in pathology and the efficacy displayed by flavonoids in canceling the effects of peroxynitrite, we decided to conduct a comparative study of three commonly used beverages with the highest polyphenol contents and proven antioxidant properties: mate (Ilex paraguariensis); green tea (Camelia sinensis) extracts and white and red wines of the main varietals. We directly evaluated and compared the extracts and wines as protein nitration inhibitors using 3-nitrotyrosine as a biomarker, we studied the extracts as protectors from OONO-induced cytotoxicity in two mammalian cell lines. Both green tea and mate extracts have a high polyphenol content, in the case of Ip, its higher concentration and higher free radical quenching activity on the DPPH assay may be mainly due to the sui generis extraction procedure. When BSA was incubated in the presence of SIN-1, a time and dose dependent nitration of the protein is clearly shown. Coincubation of BSA with Ip, green tea or red wines led to a dose dependent inhibition of the effect. Ip displayed the highest inhibitory activity, followed by red wines and the green tea. Dilutions as low as 1/1500 produced more than 80% inhibition of albumin nitration. When we studied peroxynitrite-induced cytotoxicity in murine RAW 264.7 macrophages and 31EG4 mammary cells., we found a potent, dose-dependent protective effect that was Ilex paraguariensis N red wines N green tea. Taken together, our results indicate that when the herbal preparations studied here are prepared the way they are usually drunk, Ip displays the highest inhibition of protein nitration, and the highest promotion of cell survival, whereas green tea or red wines display significant but lesser effects at the 0024-3205/$ -see front matter D (A. Gugliucci).
Journal of Cardiovascular Pharmacology, 2011
The aim of this study was to investigate the mechanisms underlying the vasorelaxant effect induced by the polyphenolic compounds found in red wine from Vale do São Francisco. In phenylephrine (10 mM) precontracted mesenteric artery rings, the red wine caused a concentration-dependent relaxation (maximum response to phenylephrine 10 mM = 87.5% 6 6.5%, n = 10). After endothelium removal, the vasorelaxant effect elicited by red wine was attenuated (28.4% 6 4.9%, n = 10). In addition, the vasorelaxant effect induced by red wine in rings pretreated with 100 mM of N w -nitro-l-arginine methyl ester and 10 mM of 1H-[1,2,4] oxadiazolo-[4,3-a]-quinoxalin-1-one was attenuated (23.4% 6 5.1%, n = 7 and 11.8% 6 2.7%, n = 6, respectively). Pretreatment with atropine did not affect the vasorelaxant effect induced by red wine (81% 6 3.9%, n = 6). Furthermore, in rabbit aortic endothelial cell line, red wine 100 and 300 mg/mL caused concentration-dependent increases in nitric oxide levels (58 6 1; 82 6 7.9; D% of fluorescence, n = 5, respectively). In conclusion, we suggest that the alcohol freelyophilized red wine induces an endothelium-dependent vasorelaxant effect due, at least in part, to a secondary increase in the concentration of nitric oxide and that this effect might be associated with phenolic compounds found in the red wine.
Red wine polyphenols induce vasorelaxation by increased nitric oxide bioactivity
Physiological research / Academia Scientiarum Bohemoslovaca, 2003
The aim of the present study was to investigate the mechanism of vasorelaxant responses induced by red wine polyphenolic compounds (Provinol). Rings of rat femoral artery with or without functional endothelium were set up in a myograph for isometric recording and precontracted with phenylephrine (10(-5) M). Provinol in cumulative doses (10(-9) to 10(-3) mg/ml) elicited endothelium- and dose-dependent relaxation of the artery with maximal relaxation of 56 per cent at the concentration of 10(-5) mg/ml. The relaxant responses to Provinol correlated well with the increase of NO synthase activity in the vascular tissue after administration of cumulative doses of Provinol (10(-9) to 10(-3) mg/ml). N(G)-nitro-L-arginine methylester (L-NAME, 3x10(-4) M) significantly attenuated the endothelium-dependent relaxation produced by Provinol. Administration of L-arginine (3x10(-5) M) restored the relaxation inhibited by L-NAME. The relaxant responses of Provinol were abolished in the presence of C...
Food & Function, 2014
Dietary polyphenols are complex, natural compounds with recognized health benefits. Initially attractive to the biomedical area due to their in vitro antioxidant properties, the biological implications of polyphenols are now known to be far from their acute ability to scavenge free radicals but rather to modulate redox signaling pathways. Actually, it is now recognized that dietary polyphenols are extensively metabolized in vivo and that the chemical, biophysical and biological properties of their metabolites are, in most cases, quite different from the ones of the parent molecules. Hence, the study of the metabolic, absorptive and signaling pathways of both phenolics and derivatives has become a major issue. In this paper we propose a short-cut for the systemic effects of polyphenols in connection with nitric oxide biology. This free radical is a ubiquitous signaling molecule with pivotal functions in vivo. It is produced through an enzymatic pathway and also through the reduction of dietary nitrate and nitrite in the human stomach. At acidic gastric pH, dietary polyphenols, in the form they are conveyed in foods and at high concentration, not only promote nitrite reduction to cNO but also embark in a complex network of chemical reactions to produce higher nitrogen oxides with signaling functions, namely by inducing posttranslational modifications. Modified endogenous molecules, such as nitrated proteins and lipids, acquire important physiological functions. Thus, local and systemic effects of cNO such as modulation of vascular tone, mucus production in the gut and protection against ischemia-reperfusion injury are, in this sense, triggered by dietary polyphenols. Evidence to support the signaling and biological effects of polyphenols by modulation of the nitrate-nitrite-NO pathway will be herein provided and discussed.
Clinical and Experimental Pharmacology and Physiology, 2003
1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NO x), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with four glasses of red wine, beer, spirits (Dutch gin) or sparkling mineral water (control) for 3 weeks. At the end of each 3 week period, serum NO x concentrations were measured just before and 1, 5 and 13 h after dinner. 3. Serum NO x concentrations were approximately 50% higher 1 and 5 h after dinner with any beverage compared with just before dinner (P = 0.0001). At 1 h after dinner, the serum NO x concentration was approximately 11% lower after dinner with alcoholic beverages compared with concentrations observed after dinner with water (P = 0.01). The fasted serum NO x concentration (13 h after dinner) was similar to the preprandial concentration and there were no differences in serum NO x concentrations between the alcoholic beverages. 4. Food intake acutely and transiently increased serum NO x concentrations, an effect that was slightly attenuated if combined with alcoholic beverages. Chronic moderate alcohol consumption had no effect on serum NO x concentration.
Red wine increases the expression of human endothelial nitric oxide synthase
Journal of the American College of Cardiology, 2003
The study tested the effect of red wine on endothelial-type nitric oxide synthase (eNOS) expression and eNOS activity in human endothelial cells. BACKGROUND Endothelial-type nitric oxide (NO) synthase exerts vasoprotective effects. Moderate alcohol consumption has been associated with a reduction of cardiovascular disease, and red wine seems to offer more benefits than any other type of drink. However, the molecular basis of this protective effect is unclear.
Food and Chemical Toxicology, 1993
Phenolic compounds and biogenic amines are known to be present in some foodstuffs which become directly genotoxic after nitrosation in vitro. Red wine has previously been shown to be genotoxic and this activity has been attributed mainly to flavonoids. Besides flavonoids, red wine contains a multiplicity of compounds, including biogenic amines. Using the Ames assay and the SOS chromotest, this study has shown that red wine and some of the nitrosatable molecules present in wine become directly genotoxic on nitrosation in vitro: these include the phenolic molecules tyramine, quercetin and malvidine-3-glucoside, whereas phenylethylamine and histamine were negative on nitrosation. Interestingly, quercetin had been predicted to be negative after nitrosation, using the CASE methodology. The concentrations of these three positive nitrosatable compounds in wine were determined by HPLC. Comparison of these concentrations and their respective levels of genotoxicity suggests that the genotoxicity after nitrosation is probably attributable to other molecules. It is also possible that synergistic effects may occur between various nitrosatable compounds in wine.