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

  • Katharina Schroecksnadel , Christiana Winkler , Barbara Wirleitner , Harald Schennach , Günter Weiss and Dietmar Fuchs
Published/Copyright: September 21, 2011

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.


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,

References

1. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999; 353:89–92.10.1016/S0140-6736(98)10279-9Search in Google Scholar

2. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339:1523–6.10.1016/0140-6736(92)91277-FSearch in 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; 341:454–7.10.1016/0140-6736(93)90206-VSearch in 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; 39:1743–50.10.1016/0006-2952(90)90120-ASearch in Google Scholar

5. Granados-Soto V. Pleiotropic effects of resveratrol. Drug News Perspect 2003; 16:299–307.10.1358/dnp.2003.16.5.829318Search in Google 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; 107:141–5.10.1016/S0049-3848(02)00273-6Search in Google Scholar

7. Falchetti R, Fuggetta MP, Lanzilli G, Tricarico M, Ravagnan G. Effects of resveratrol on human immune cell function. Life Sci 2001; 70:81–96.10.1016/S0024-3205(01)01367-4Search in Google Scholar

8. Libby P. Inflammation in atherosclerosis. Nature 2002; 420:868–74.10.1038/nature01323Search in Google Scholar PubMed

9. Young JL, Libby P, Schonbeck U. Cytokines in the pathogenesis of atherosclerosis. Thromb Haemost 2002; 88:554–67.10.1055/s-0037-1613256Search in 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; 104:2673–8.10.1161/hc4601.099485Search in Google Scholar PubMed

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; 274:1049–57.10.1001/jama.1995.03530130055028Search in 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; 106:263–71.10.1016/0021-9150(94)90131-7Search in 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; 93:627–9.10.1016/j.amjcard.2003.11.035Search in Google 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; 14:82–7.10.1515/pteridines.2003.14.3.82Search in Google Scholar

15. Schroecksnadel K, Frick B, Winkler C, Leblhuber F, Wirleitner B, Fuchs D. Hyperhomocysteinemia and immune activation. Clin Chem Lab Med 2003; 41:1438–43.10.1515/CCLM.2003.221Search in Google 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; 134:53–6.10.1046/j.1365-2249.2003.02251.xSearch in 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.10.1515/CCLM.2005.234Search in 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; 62:155–60.10.1111/j.1365-3083.2005.01654.xSearch in Google 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; 100:159–63.10.1016/j.imlet.2005.03.008Search in 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; 331:19–23.10.1016/S0009-8981(03)00076-7Search in 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; 131:264–7.10.1046/j.1365-2249.2003.02021.xSearch in 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; 62:1299–308.10.1016/S0006-2952(01)00775-4Search in 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.Search in 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; 7:834–42.10.1038/sj.cdd.4400719Search in Google Scholar PubMed

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; 15:1613–5.10.1096/fj.00-0675fjeSearch in Google Scholar PubMed

26. Losa GA. Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. Eur J Clin Invest 2003; 33:818–23.10.1046/j.1365-2362.2003.01219.xSearch in Google Scholar PubMed

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; 49:51–4.10.1055/s-2007-969810Search in Google Scholar PubMed

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.Search in 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; 66:2427–35.10.1016/j.bcp.2003.08.008Search in Google Scholar PubMed

30. Halliwell B, Zhao K, Whiteman M. The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 2000; 33:819–30.10.1080/10715760000301341Search in Google Scholar PubMed

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; 64:973–7.10.1016/j.mehy.2004.11.011Search in Google Scholar PubMed

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.10.1093/ajcn/81.1.268SSearch in Google Scholar PubMed

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; 78:334–8.10.1093/ajcn/78.2.334Search in Google Scholar PubMed

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; 77:826–33.10.1093/ajcn/77.4.826Search in Google Scholar PubMed

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; 56:608–14.10.1038/sj.ejcn.1601365Search in Google Scholar PubMed

Published Online: 2011-9-21
Published in Print: 2005-10-1

©2005 by Walter de Gruyter Berlin New York

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  1. Homocysteine research – where do we stand and where are we going?
  2. Hyperhomocysteinemia and arteriosclerosis: historical perspectives
  3. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
  4. Homocysteine and vascular disease in diabetes: a double hit?
  5. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
  6. Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
  7. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
  8. Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
  9. Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
  10. Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
  11. Hyperhomocysteinemia and macromolecule modifications in uremic patients
  12. Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
  13. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
  14. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
  15. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
  16. A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
  17. Betaine: a key modulator of one-carbon metabolism and homocysteine status
  18. Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
  19. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
  20. Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
  21. Homocysteine and B vitamins in mild cognitive impairment and dementia
  22. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
  23. Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
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  25. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
  26. Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
  27. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
  28. Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
  29. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
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