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l-carnitine modulates blood platelet oxidative stress

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Abstract

The oxidative stress induced by acute exertion may interfere with blood platelet activation. The beneficial effect of l-carnitine (γ-trimethylamino-β-hydroxybutyric acid) on oxidative stress in blood platelets has not been fully investigated; however, different studies indicate that this compound modulates platelet functions. The aim of our study was to assess the effects of l-carnitine on platelet activation and oxidative/nitrative protein damage (determined by the levels of protein carbonyl groups, thiol groups, and 3-nitrotyrosine residues) in resting blood platelets or platelets treated with peroxynitrite (ONOO−, a strong physiological oxidant) in vitro. We also investigated the effects of l-carnitine on the level of platelet glutathione and on the formation of superoxide anion radicals \( \left( {{\hbox{O}}_2^{ - \bullet }} \right) \), lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) in blood platelets stimulated by thrombin (a strong physiological agonist), and platelet aggregation induced by adenosine diphosphate (a strong physiological stimulator). We have observed that carnitine decreases platelet activation (measured by platelet aggregation, the generation of \( {\hbox{O}}_2^{ - \bullet } \), and TBARS production). Moreover, our results in vitro demonstrate that carnitine may protect against oxidation of thiol groups induced by ONOO−. Thus, carnitine may have some protectory effects against oxidative changes induced in blood platelets.

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References

  • Alessio HM. Exercise-induced oxidative stress. Med Sci Sports Exer. 1993;25:218–24.

    CAS  Google Scholar 

  • Ando Y, Steiner M. Sulfhydryl and disulfide groups of platelet membranes: determination of disulfide groups. Biochim Biophys Acta. 1973a;311:26–37.

    Article  CAS  PubMed  Google Scholar 

  • Ando Y, Steiner M. Sulfhydryl and disulfide groups of platelet membranes: determination of sulfhydryl groups. Biochim Biophys Acta. 1973b;311:38–44.

    Article  CAS  PubMed  Google Scholar 

  • Bald E, Chwatko G, Glowacki R, Kuśmierek K. Analysis of plasma thiols by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 2004;1032:109–15.

    Article  CAS  Google Scholar 

  • Bartosz G. Peroxynitrite: mediator of the toxic action of nitric oxide. Acta Biochim Pol. 1996;43:645–59.

    CAS  PubMed  Google Scholar 

  • Begonja AJ, Gambaryan S, Geiger J, Aktas B, Pozgajova M, Nieswandt B, et al. NAD(P)H oxidase-generated ROS production regulates {alpha}IIb{beta}3 integrin activation independent of the NO/cGMP pathway. Blood. 2005;106:2757–60.

    Article  CAS  PubMed  Google Scholar 

  • Bloomer RJ, Smith WA. Oxidative stress in response to aerobic and anaerobic power testing: influence of exercise training and carnitine supplementation. Res Sports Med. 2009;1:1–16.

    Article  Google Scholar 

  • Bonomini M, Sirolli V, Dottori S, Amoroso L, Di Liberato L, Arduini A. l-carnitine inhibits a subset of platelet activation responses in chronic uraemia. Nephrol Dial Transplant. 2007;22:2623–9.

    Article  CAS  PubMed  Google Scholar 

  • Brevetti G, Chiariello M, Ferulano G, Policicchio A, Nevola E, Rossini A, et al. Increases in walking distance in patients with peripheral vascular disease treated with l-carnitine: a double-blind, cross-over study. Circulation. 1988;77:767–73.

    CAS  PubMed  Google Scholar 

  • Broquist HP, Borum PR. Carnitine biosynthesis: nutritional implications. Adv Nutr Res. 1982;4:181–204.

    CAS  PubMed  Google Scholar 

  • Buczynski A, Kedziora J, Tkaczewski W, Wachowicz B. Effect of submaximal physical exercise on antioxidative protection of human blood platelets. Int J Sports Med. 1991;12:52–4.

    Article  CAS  PubMed  Google Scholar 

  • Buss H, Chan TP, Sluis KB, Domigan NM, Winterbourn CC. Protein carbonyl measurement by a sensitive ELISA method. Free Radic Biol Med. 1997;23:361–6.

    Article  CAS  PubMed  Google Scholar 

  • Cerretelli P, Marconi C. l-carnitine supplementation in humans. The effects on physical performance. Int J Sports Med. 1990;11:1–14.

    Article  CAS  PubMed  Google Scholar 

  • Chen JQ, Cammarata PR, Baines CP, Yager JD. Regulation of mitochondrial respiratory chain biogenesis by estrogens/ estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta. 2009;1793:1540–70.

    Article  CAS  PubMed  Google Scholar 

  • Cheung P, Salas E, Schulz R, Radomski M. Nitric oxide and platelet function: implications for neonatology. Semin Perinatol. 2003;21:409–17.

    Article  Google Scholar 

  • Di Massimo C, Scarpelli P, Tozzi-Ciancarelli MG. Possible involvement of oxidative stress in exercise-mediated platelet activation. Clin Hemorheol Microcirc. 2004;30:313–6.

    PubMed  Google Scholar 

  • Eiserich JP, Patel RP, OÕDonnell VB. Pathophysiology of nitric oxide and related species: free radical reactions and modification of biomolecules. Mol Aspects Med. 1998;19:221–357.

    Article  CAS  PubMed  Google Scholar 

  • El-Sayed MS, Ali N, El-Sayed Ali Z. Aggregation and activation of blood platelets in exercise and training. Sports Med. 2005;35:11–22.

    Article  PubMed  Google Scholar 

  • Essex DW, Li M. Redox control of platelet aggregation. Biochemistry. 2003;42:129–36.

    Article  CAS  PubMed  Google Scholar 

  • Ficicilar H, Zergeroglu AM, Ersoz G, Erdogan A, Ozdemir S, Tekin D. The effects of short-term training on platelet functions and total antioxidant capacity in rats. Physiol Res. 2006;55:151–6.

    CAS  PubMed  Google Scholar 

  • Forde RC, Fitzgerald DJ. Reactive oxygen species and platelet activation in reperfusion injury. Circulation. 1997;95:787–9.

    CAS  PubMed  Google Scholar 

  • Gawaz M, Langer H, May E. Platelets in inflammation and atherogenesis. J Clin Invest. 2005;115:3378–84.

    Article  CAS  PubMed  Google Scholar 

  • Glowacki R, Wójcik K, Bald E. Facile and sensitive method for the determination of mesna in plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 2001;914:29–35.

    Article  CAS  Google Scholar 

  • Głód BK, Kowalski C. Free radicals and their analysis using high performance liquid chromatography. Pol J Food Nutr Sci. 2004;13:23–8.

    Google Scholar 

  • Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol. 2004;561:1–25.

    Article  CAS  PubMed  Google Scholar 

  • Hellsten Y, Ahlborg G, Jensen-Urstad M, Sjodin B. Indication of in vivo xanthine oxidase activity in human skeletal muscle during exercise in man. Acta Physiol Scand. 1988;137:159–60.

    Article  Google Scholar 

  • Hellsten Y, Hansson HA, Johnson L, Frandsen U, Sjodin B. Increased expression of xanthine oxidase and insulin-like growth factor I (IGF-I) immunoreactivity in skeletal muscle after strenuous exercise in humans. Acta Physiol Scand. 1996;157:191–7.

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Hernandez A, Anchez-Yague J, Martin-Valmaseda EM, Llanillo M. Oxidative inactivation of human and sheep platelet membrane-associated phosphotyrosine phosphatase activity. Free Radic Biol Med. 1999;26:1218–30.

    Article  CAS  PubMed  Google Scholar 

  • Ischiropoulos H. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem Biophys Res Commun. 2003;305:776–83.

    Article  CAS  PubMed  Google Scholar 

  • Jahn B, Hansch GM. Oxygen radical generation in human platelets: dependence of 12-lipoxygenase activity and on the glutathione cycle. Int Arch Allergy Appl Immunol. 1990;93:73–9.

    Article  CAS  PubMed  Google Scholar 

  • Jane E, Freedman MD. Molecular regulation of platelet-dependent thrombosis. Circulation. 2005;112:2725–34.

    Article  Google Scholar 

  • Karlic H, Lohninger A. Supplementation of l-carnitine in athletes: does it make sense? Nutrition. 2004;20:709–15.

    Article  CAS  PubMed  Google Scholar 

  • Khan J, Brennan DM, Bradley N, Gao B, Bruckdorfer R, Jacobs M. 3-Nitrotyrosine in the proteins of human plasma determined by an ELISA method. Biochem J. 1998;330:795–801.

    CAS  PubMed  Google Scholar 

  • Kingwell BA. Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease. FASEB J. 2000;14:1685–96.

    Article  CAS  PubMed  Google Scholar 

  • Lohninger A, Pittner G, Pittner F. l-carnitine: new aspects of a known compound—a brief survey. Monatsh Chem. 2005;136:1255–68.

    Article  CAS  Google Scholar 

  • Lufrano M, Balazy M. Interactions of peroxynitrite and other nitrating substances with human platelets: the role of glutathione and peroxynitrite permeability. Biochem Pharmacol. 2003;65:515–23.

    Article  CAS  PubMed  Google Scholar 

  • Lundblad RL, White GC. The interaction of thrombin with blood platelets. Platelets. 2005;16:373–82.

    Article  CAS  PubMed  Google Scholar 

  • Maiorana A, O'Driscoll G, Taylor R, Green D. Exercise and the nitric oxide vasodilator system. Sports Med. 2003;33:1013–35.

    Article  PubMed  Google Scholar 

  • McBride JM, Kraemer WJ, Triplett-McBride NT, Sebastianelli W. The effect of resistance exercise on free radical production. Med Sci Sports Exerc. 1998;30:67–72.

    CAS  PubMed  Google Scholar 

  • McBride JM, Radzwich R, Mangino L, McCormick M, Mc-Cormick T, Volek JS, et al. Responses of serum creatine kinase activity to heavy resistance exercise in endurance and recreationally trained women. J Strength Cond Res. 1995;9:139–42.

    Article  Google Scholar 

  • Michno A, Raszeja-Specht A, Jankowska-Kulawy A, Pawelczyk T, Szutowicz A. Effect of l-carnitine on acetyl-CoA content and activity of blood platelets in healthy and diabetic persons. Clin Chem. 2005;51:1673–82.

    Article  CAS  PubMed  Google Scholar 

  • Miller DM, Grover TA, Nayini N, Aust SD. Xantine-oxidase- and iron-dependent lipid peroxidation. Arch Biochem Biophys. 1993;301:1–7.

    Article  CAS  PubMed  Google Scholar 

  • Olas B, Żbikowska HM, Wachowicz B, Krajewski T, Buczynski A, Magnuszewska A. Inhibitory effect of resveratrol on free radical generation in blood platelets. Acta Biochim Pol. 1999;46:991–6.

    Google Scholar 

  • Olas B, Nowak P, Kołodziejczyk J, Wachowicz B. The effects of antioxidants on peroxynitrite-induced changes in platelet proteins. Thromb Res. 2004;113:399–406.

    Article  CAS  PubMed  Google Scholar 

  • Olas B, Wachowicz B, Majsterek I, Błasiak J, Stochmal A, Oleszek W. Antioxidant properties of trans-3,3′,5, 5′-tetrahydroxy-4-4′methoxystilbene against modification of different biomolecules in human cells treated with platinum compounds. Nutrition. 2006;22:1202–9.

    Article  CAS  PubMed  Google Scholar 

  • Olas B, Wachowicz B. Role of reactive nitrogen species in blood platelet functions. Platelets. 2007;18:555–65.

    Article  CAS  PubMed  Google Scholar 

  • Pignatelli P, Pulcinelli FM, Lenti L, Gazzaniga PP, Violi F. Hydrogen peroxide is involved in collagen-induced platelet activation. Blood. 1998;91:484–90.

    CAS  PubMed  Google Scholar 

  • Pignatelli P, Lenti L, Sanguigni V, Frati G, Simeoni I, Gazzaniga PP, et al. Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress. Am J Physiol Heart Circ Physiol. 2003;284:41–8.

    Google Scholar 

  • Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol. 1995;268:L699–722.

    CAS  PubMed  Google Scholar 

  • Sabetkar M, Low SY, Naseem KM, Bruckdorfer KR. The nitration of proteins in platelets: significance in platelet function. Free Radic Biol Med. 2002;33:728–36.

    Article  CAS  PubMed  Google Scholar 

  • Singh I, Quinn H, Mok M, Southgate RJ, Turner AH, Li D, et al. The effect of exercise and training status on platelet activation: do cocoa polyphenols play a role? Platelets. 2006;17:361–7.

    Article  CAS  PubMed  Google Scholar 

  • Soszynski M, Bartosz G. Effect of peroxynitrite on erythrocytes. Biochim Biophys Acta. 1996;1291:107–14.

    PubMed  Google Scholar 

  • Spinelli SL, Brien JJ, Bancos S, Lehmann GM, Springer DL, Blumberg N, et al. The PPAR–platelet connection: modulators of inflammation and potential cardiovascular effects. PPAR Res. 2008;1:1–16.

    Article  Google Scholar 

  • Triggiani M, Oriente A, Golino P, Gentile M, Battaglia C, Brevetti G, et al. Inhibition of platelet-activating factor synthesis in human neutrophils and platelets by propionyl-l-carnitine. Biochem Pharmacol. 1999;58:1341–8.

    Article  CAS  PubMed  Google Scholar 

  • Turgay M, Durak I, Erten S, Ertugrul E, Devrim E, Avci A, et al. Oxidative stress and antioxidant parameters in a Turkish group of patients with active and inactive systemic lupus erythematosus. APLAR J Rheumat. 2007;10:101–6.

    Article  Google Scholar 

  • Volek JS, Kramer WJ, Rubin MR, Gomez AL, Ratamess NA, Gaynor P. l-carnitine L-tartrate supplementation favorably affects markers of recovery from exercise stress. Am J Physiol Endocrinol Metab. 2002;282:E474–82.

    CAS  PubMed  Google Scholar 

  • Wachowicz B. Adenine nucleotides in thrombocytes of birds. Cell Biochem Funct. 1984;2:167–70.

    Article  CAS  PubMed  Google Scholar 

  • Wachowicz B, Kustroń J. Effect of cisplatin on lipid peroxidation in pig blood platelets. Cytobios. 1992;70:41–7.

    CAS  PubMed  Google Scholar 

  • Wachowicz B, Olas B, Zbikowska HM, Buczynski A. Generation of reactive oxygen species in blood platelets. Platelets. 2002;13:175–82.

    Article  CAS  PubMed  Google Scholar 

  • Walkowiak B, Michalak E, Koziołkiewicz W, Cierniewski CS. Rapid photometric method for estimation of platelet count in blood plasma or platelet suspension. Thromb Res. 1989;56:763–6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

This work was supported by grant 505/374 from the University of Lodz.

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Authors and Affiliations

  1. Department of General Biochemistry, Institute of Biochemistry, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland

    Joanna Saluk-Juszczak, Beata Olas & Barbara Wachowicz

  2. Department of Environmental Chemistry, University of Lodz, Pomorska 163, 90-236, Lodz, Poland

    Rafal Glowacki & Edward Bald

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  1. Joanna Saluk-Juszczak
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  2. Beata Olas
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Correspondence to Joanna Saluk-Juszczak.

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Saluk-Juszczak, J., Olas, B., Wachowicz, B. et al. l-carnitine modulates blood platelet oxidative stress. Cell Biol Toxicol 26, 355–365 (2010). https://doi.org/10.1007/s10565-009-9148-4

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