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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

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1437-4331
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Volume 43, Issue 10 (Oct 2005)

Issues

Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro

Katharina Schroecksnadel
  • Division of Biological Chemistry, Biocentre, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Christiana Winkler
  • Division of Biological Chemistry, Biocentre, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Barbara Wirleitner
  • Division of Biological Chemistry, Biocentre, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Harald Schennach
  • Central Institute of Blood Transfusion and Immunology, University Hospital, Innsbruck, Austria
  • Other articles by this author:
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/ Günter Weiss / Dietmar Fuchs
  • Division of Biological Chemistry, Biocentre, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2011-09-21 | DOI: https://doi.org/10.1515/CCLM.2005.189

Abstract

Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10–100μM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.

Keywords: homocysteine; immune activation; peripheral blood mononuclear cells (PBMC); resveratrol

References

  • 1.

    Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999; 353:89–92.Google Scholar

  • 2.

    Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339:1523–6.Google Scholar

  • 3.

    Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993; 341:454–7.Google Scholar

  • 4.

    de Whalley CV, Rankin SM, Hoult JR, Jessup W, Leake DS. Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages. Biochem Pharmacol 1990; 39:1743–50.Google Scholar

  • 5.

    Granados-Soto V. Pleiotropic effects of resveratrol. Drug News Perspect 2003; 16:299–307.CrossrefGoogle Scholar

  • 6.

    Olas B, Wachowicz B, Saluk-Juszczak J, Zielinski T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb Res 2002; 107:141–5.Google Scholar

  • 7.

    Falchetti R, Fuggetta MP, Lanzilli G, Tricarico M, Ravagnan G. Effects of resveratrol on human immune cell function. Life Sci 2001; 70:81–96.Google Scholar

  • 8.

    Libby P. Inflammation in atherosclerosis. Nature 2002; 420:868–74.Google Scholar

  • 9.

    Young JL, Libby P, Schonbeck U. Cytokines in the pathogenesis of atherosclerosis. Thromb Haemost 2002; 88:554–67.Google Scholar

  • 10.

    Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104:2673–8.Google Scholar

  • 11.

    Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. J Am Med Assoc 1995; 274:1049–57.Google Scholar

  • 12.

    Weiss G, Willeit J, Kiechl S, Fuchs D, Jarosch E, Oberhollenzer F, et al. Increased concentrations of neopterin in carotid atherosclerosis. Atherosclerosis 1994; 106:263–71.Google Scholar

  • 13.

    Avanzas P, Arroyo-Espliguero R, Cosin-Sales J, Quiles J, Zouridakis E, Kaski JC. Prognostic value of neopterin levels in treated patients with hypertension and chest pain but without obstructive coronary artery disease. Am J Cardiol 2004; 93:627–9.CrossrefGoogle Scholar

  • 14.

    Frick B, Rudzite V, Schröcksnadel K, Kalnins U, Erglis A, Trusinskis K, et al. Homocysteine, B vitamins and immune activation in coronary heart disease. Pteridines 2003; 14:82–7.CrossrefGoogle Scholar

  • 15.

    Schroecksnadel K, Frick B, Winkler C, Leblhuber F, Wirleitner B, Fuchs D. Hyperhomocysteinemia and immune activation. Clin Chem Lab Med 2003; 41:1438–43.CrossrefGoogle Scholar

  • 16.

    Schroecksnadel K, Frick B, Wirleitner B, Schennach H, Fuchs D. Homocysteine accumulates in supernatants of stimulated human peripheral blood mononuclear cells. Clin Exp Immunol 2003; 134:53–6.Google Scholar

  • 17.

    Schroecksnadel K, Frick B, Winkler C, Wirleitner B, Weiss G, Fuchs D. Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells. Pteridines 2005. In press.Google Scholar

  • 18.

    Schroecksnadel K, Frick B, Winkler C, Wirleitner B, Schennach H, Fuchs D. Aspirin down-regulates homocysteine formation in stimulated human peripheral blood mononuclear cells. Scand J Immunol 2005; 62:155–60.CrossrefGoogle Scholar

  • 19.

    Wirleitner B, Schroecksnadel K, Winkler C, Schennach H, Fuchs D. Resveratrol suppresses interferon-gamma-induced biochemical pathways in human peripheral blood mononuclear cells in vitro. Immunol Lett 2005; 100:159–63.Google Scholar

  • 20.

    Frick B, Schroecksnadel K, Neurauter G, Wirleitner B, Artner-Dworzak E, Fuchs D. Rapid measurement of total plasma homocysteine by HPLC. Clin Chim Acta 2003; 331:19–23.Google Scholar

  • 21.

    Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Atorvastatin suppresses interferon-gamma-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol 2003; 131:264–7.Google Scholar

  • 22.

    Gao X, Xu YX, Janakiraman N, Chapman RA, Gautam SC. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochem Pharmacol 2001; 62:1299–308.Google Scholar

  • 23.

    Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52:673–751.Google Scholar

  • 24.

    Bernhard D, Tinhofer I, Tonko M, Hubl H, Ausserlechner MJ, Greil R, et al. Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells. Cell Death Differ 2000; 7:834–42.CrossrefGoogle Scholar

  • 25.

    Tinhofer I, Bernhard D, Senfter M, Anether G, Loeffler M, Kroemer G, et al. Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J 2001; 15:1613–5.Google Scholar

  • 26.

    Losa GA. Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. Eur J Clin Invest 2003; 33:818–23.CrossrefGoogle Scholar

  • 27.

    Kimura Y, Ohminami H, Okuda H, Baba K, Kozawa M, Arichi S. Effects of stilbene components of roots of Polygonum ssp. on liver injury in peroxidized oil-fed rats. Planta Med 1983; 49:51–4.Google Scholar

  • 28.

    Bertelli AA, Giovannini L, Stradi R, Bertelli A, Tillement JP. Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4′,5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats. Int J Tissue React 1996; 18:67–71.Google Scholar

  • 29.

    Gao X, Deeb D, Media J, Divine G, Jiang H, Chapman RA, et al. Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects. Biochem Pharmacol 2003; 66:2427–35.Google Scholar

  • 30.

    Halliwell B, Zhao K, Whiteman M. The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 2000; 33:819–30.Google Scholar

  • 31.

    Murr C, Schroecksnadel K, Winkler C, Ledochowski M, Fuchs D. Antioxidants may increase the probability of developing allergic diseases and asthma. Med Hypotheses 2005; 64:973–7.CrossrefGoogle Scholar

  • 32.

    Halliwell B, Rafter J, Jenner A. health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidants or not? Am J Clin Nutr 2005; 81(Suppl):268S–76S.Google Scholar

  • 33.

    Mennen LI, de Courcy GP, Guilland JC, Ducros V, Zarebska M, Bertrais S, et al. Relation between homocysteine concentrations and the consumption of different types of alcoholic beverages: the French Supplementation with Antioxidant Vitamins and Minerals Study. Am J Clin Nutr 2003; 78:334–8.Google Scholar

  • 34.

    Ganji V, Kafai MR. Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2003; 77:826–33.Google Scholar

  • 35.

    Dixon JB, Dixon ME, O'Brien PE. Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status. Eur J Clin Nutr 2002; 56:608–14.Google Scholar

About the article

Corresponding author: Dietmar Fuchs, Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Str. 3, 6020 Innsbruck, Austria Phone: +43-512-507-3519, Fax: +43-512-507-2865,


Published Online: 2011-09-21

Published in Print: 2005-10-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2005.189.

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