Free Radicals and Antioxidants in Human Disease

  • Michael Lawson
  • Klaudia Jomova
  • Patrik Poprac
  • Kamil Kuča
  • Kamil Musílek
  • Marian ValkoEmail author


Free radicals are species containing one or more unpaired electrons. Unpaired or free electrons are responsible for enhanced reactivity of free radicals with various biomolecules. Most frequently occurring radicals in biological systems are reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS are generated by the tightly regulated enzymes, nicotinamide adenine dinucleotide phosphate oxidase isoforms and nitric oxide synthases. Overproduction of ROS and RNS results in oxidative and nitrosative stress, a state which is responsible for the damage to cell macromolecules including lipids, proteins and DNA. Oxidative stress has been implicated in the aetiology of various disease states of an organism. In this chapter, we discuss the biochemistry of free radicals and their impact on the development of various diseases. Organs of biological systems are the principal targets of oxidant species, which are implicated in atherosclerosis, diabetes, carcinogenesis and neurodegeneration. Attention is focused on oxidative stress-induced cardiovascular disease, type 2 diabetes, cancer and Alzheimer’s disease. The roles of redox active metal-catalysed formation of ROS and antioxidants in protection against oxidative damage is also discussed.


Free radicals Oxidative stress Antioxidants Human disease 



This work was supported by the Scientific Grant Agency (VEGA Project 1/0686/17), Research and Development Support Agency (APVV-15-079), Grant Agency of Constantine Philosopher University in Nitra (UGA Project #VII/6/2014) and European Community under project #26220220180: Building Research Centre “AgroBioTech”. The authors would like to acknowledge the long-term development plan of FNHK and UHK.


  1. Araujo M, Wilcox CS. Oxidative stress in hypertension: role of the kidney. Antioxid Redox Signal. 2014;20:74–101.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bast A, Haenen GR. Ten misconceptions about antioxidants. Trends Pharmacol Sci. 2013;34:430–6.CrossRefPubMedGoogle Scholar
  3. Behrend L, Henderson G, Zwacka RM. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans. 2003;31:1441–4.CrossRefPubMedGoogle Scholar
  4. Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004;555:589–606.CrossRefPubMedGoogle Scholar
  5. Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol. 2015;36:161–78.CrossRefPubMedGoogle Scholar
  6. Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51:2796–803.CrossRefPubMedGoogle Scholar
  7. Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys. 1993;300:535–43.CrossRefPubMedGoogle Scholar
  8. Butler J. Thermodynamic considerations of free radical reactions. In: Rhodes CJ, editor. Toxicology of the human environment. London: Taylor and Francis; 2000. p. 437–53.Google Scholar
  9. Cadenas E, Davies KJA. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29:222–30.CrossRefPubMedGoogle Scholar
  10. Cadet J, Douki T, Pouget JP, Ravanat JL. Singlet oxygen DNA damage products: formation and measurement. Methods Enzymol. 2000;319:143–53.CrossRefPubMedGoogle Scholar
  11. Carr AC, McCall MR, Frei B. Oxidation of LDL by myeloperoxidase and reactive nitrogen species - reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol. 2000;20:1716–23.CrossRefPubMedGoogle Scholar
  12. Chan AC. Partners in defense, vitamin E and vitamin C. Can J Physiol Pharmacol. 1993;71:725–31.CrossRefPubMedGoogle Scholar
  13. Chu FF, Esworthy RS, Doroshow JH. Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer. Free Radic Biol Med. 2004;36:1481–95.CrossRefPubMedGoogle Scholar
  14. Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT, Atwood CS, Huang X, et al. Evidence that the beta-amyloid plaques of Alzheimer’s disease represent the redox-silencing and entombment of abeta by zinc. J Biol Chem. 2000;275:19439–42.CrossRefPubMedGoogle Scholar
  15. Cuajungco MP, Frederickson CJ, Bush AI. Amyloid-beta metal interaction and metal chelation. Subcell Biochem. 2005;38:235–54.CrossRefPubMedGoogle Scholar
  16. Damianaki A, Bakogeorgou E, Kampa M, Notas G, Hatzoglou A, Panagiotou S, Gemetzi C, et al. Potent inhibitory action of red wine polyphenolson human breast cancer cells. J Cell Biochem. 2000;78:429–41.CrossRefPubMedGoogle Scholar
  17. Dikalov SI, Vitek MP, Mason RP. Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical. Free Radic Biol Med. 2004;36:340–7.CrossRefPubMedGoogle Scholar
  18. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med. 2002;32:1102–15.CrossRefPubMedGoogle Scholar
  19. Dreher D, Junod AF. Role of oxygen free radicals in cancer development. Eur J Cancer. 1996;32A:30–8.CrossRefPubMedGoogle Scholar
  20. Enami S, Sakamoto Y, Colussi AJ. Fenton chemistry at aqueous interfaces. Proc Natl Acad Sci U S A. 2014;111:623–8.CrossRefPubMedGoogle Scholar
  21. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes. 2003;52:1–8.CrossRefPubMedGoogle Scholar
  22. Flynn JM, Melov S. SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic Biol Med. 2013;62:4–12.CrossRefPubMedGoogle Scholar
  23. Fu S, Fu MX, Baynes JW, Thorpe SR, Dean RT. Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs): amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins. Biochem J. 1998;330:233–9.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Ghafourifar P, Cadenas E. Mitochondrial nitric oxide synthase. Trends Pharmacol Sci. 2005;26:190–5.CrossRefPubMedGoogle Scholar
  25. Giuffrè A, Borisov VB, Arese M, Sarti P, Forte E. Cytochrome bd oxidase and bacterial tolerance to oxidative and nitrosative stress. Biochim Biophys Acta. 2014;1837:1178–87.CrossRefPubMedGoogle Scholar
  26. Grankvist K, Marklund SL, Taljedal IB. CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione-peroxidase in pancreatic-islets and other tissues in the mouse. Biochem J. 1981;199:393–8.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Gruetter DY, Gruetter CA, Barry BK, Baricos WH, Hyman AL, Kadowitz PJ, Ignarro LJ. Activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside, and nitrosoguanidine—inhibition by calcium, lanthanum, and other cations, enhancement by thiols. Biochem Pharmacol. 1980;29:2943–50.CrossRefPubMedGoogle Scholar
  28. Gustafson B, Hedjazifar S, Gogg S, Hammarstedt A, Smith U. Insulin resistance and impaired adipogenesis. Trends Endocrinol Metab. 2015;26:193–200.CrossRefPubMedGoogle Scholar
  29. Gutteridge JM, Rowley DA, Halliwell B, Westermarck T. Increased non-protein-bound iron and decreased protection against superoxide-radical damage in cerebrospinal fluid from patients with neuronal ceroid lipofuscinoses. Lancet. 1982;2:459–60.CrossRefPubMedGoogle Scholar
  30. Halliwell B, Gutteridge JMC. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990;186:1–85.CrossRefPubMedGoogle Scholar
  31. Hare JM, Stamler JS. NO/redox disequilibrium in the failing heart and cardiovascular system. J Clin Invest. 2005;115:509–17.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hayashi H, Iimuro M, Matsumoto Y, Kaneko M. Effects of gamma-glutamylcysteine ethyl ester on heart mitochondrial creatine kinase activity: involvement of sulfhydryl groups. Eur J Pharmacol. 1998;349:133–6.CrossRefPubMedGoogle Scholar
  33. Hink U, Li HG, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001;88:E14–22.CrossRefPubMedGoogle Scholar
  34. Hua Y, Robinson TJ, Cao Y, Shi GP, Ren J, Nair S. Cathepsin K knockout alleviates aging-induced cardiac dysfunction. Aging Cell. 2015;14:345–51.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, et al. Cu(II) potentiation of Alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem. 1999;274:37111–6.CrossRefPubMedGoogle Scholar
  36. Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem. 2003;10:2495–505.CrossRefPubMedGoogle Scholar
  37. Jensen GL, Meister A. Radioprotection of human lymphoid cells by exogenously supplied glutathione is mediated by gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1983;80:4714–7.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Jürgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A. 1998;95:4997–5002.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Kaneko M, Elimban V, Dhalla NS. Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. Am J Phys. 1989;257:H804–11.Google Scholar
  40. Kaneto H, Kajimoto Y, Fujitani Y, Matsuoka T, Sakamoto K, Matsuhisa M, Yamasaki Y, et al. Oxidative stress induces p21 expression in pancreatic islet cells: possible implication in beta-cell dysfunction. Diabetologia. 1999;42:1093–7.CrossRefPubMedGoogle Scholar
  41. Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol. 2004;44:239–67.CrossRefPubMedGoogle Scholar
  42. Koff JL, Ramachandiran S, Bernal-Mizrachi L. A time to kill: targeting apoptosis in cancer. Int J Mol Sci. 2015;16:2942–55.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kovacic P, Jacintho JD. Mechanisms of carcinogenesis: focus on oxidative stress and electron transfer. Curr Med Chem. 2001;8:773–96.CrossRefPubMedGoogle Scholar
  44. Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St-Pierre J, Grey ST, , Lowell BB. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 2003;112:1831–1842.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Kuka S, Tatarkova Z, Racay P, Lehotsky J, Dobrota D, Kaplan P. Effect of aging on formation of reactive oxygen species by mitochondria of rat heart. Gen Physiol Biophys. 2013;32:415–20.CrossRefPubMedGoogle Scholar
  46. Kukreja RC, Hess ML. The oxygen free radical system: from equations through membrane-protein interactions to cardiovascular injury and protection. Cardiovasc Res. 1992;26:641–55.CrossRefPubMedGoogle Scholar
  47. Kwong LK, Sohal RS. Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria. Arch Biochem Biophys. 1998;350:118–26.CrossRefPubMedGoogle Scholar
  48. Landis GN, Tower J. Superoxide dismutase evolution and life span regulation. Mech Ageing Dev. 2005;126:365–79.CrossRefPubMedGoogle Scholar
  49. Lawlor MA, Alessi DR. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci. 2001;114:2903–10.PubMedGoogle Scholar
  50. Li HG, Forstermann U. Nitric oxide in the pathogenesis of vascular disease. J Pathol. 2000;190:244–54.CrossRefPubMedGoogle Scholar
  51. Li JM, Shah AM. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol. 2003;14:S221–6.CrossRefPubMedGoogle Scholar
  52. Li FJ, Shen L, Ji HF. Dietary intakes of vitamin E, vitamin C, and β-carotene and risk of Alzheimer’s disease: a meta-analysis. J Alzheimers Dis. 2012;31:253–8.PubMedGoogle Scholar
  53. Ling X, Nagai R, Sakashita N, Takeya M, Horiuchi S, Takahashi K. Immunohistochemical distribution and quantitative biochemical detection of advanced glycation end products in fetal to adult rats and in rats with streptozotocin-induced diabetes. Labor Invest. 2001;81:845–61.CrossRefGoogle Scholar
  54. Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000;21:361–70.CrossRefPubMedGoogle Scholar
  55. McCord JM, Fridovich I. Superoxide dismutases: you’ve come a long way, baby. Antioxid Redox Signal. 2014;20:1548–9.CrossRefPubMedGoogle Scholar
  56. Milkovic L, Siems W, Siems R, Zarkovic N. Oxidative stress and antioxidants in carcinogenesis and integrative therapy of cancer. Curr Pharm Des. 2014;20:6529–42.CrossRefPubMedGoogle Scholar
  57. Molavi B, Mehta JL. Oxidative stress in cardiovascular disease: molecular basis of its deleterious effects, its detection, and therapeutic considerations. Curr Opin Cardiol. 2004;19:488–93.CrossRefPubMedGoogle Scholar
  58. Mortensen A, Skibsted LH, Truscott TG. The interaction of dietary carotenoids with radical species. Arch Biochem Biophys. 2001;385:13–9.CrossRefPubMedGoogle Scholar
  59. Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ. Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells. J Biol Chem. 2003;278:31426–33.CrossRefPubMedGoogle Scholar
  60. Nishikawa T, Edelstei D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000;404:787–90.CrossRefPubMedGoogle Scholar
  61. Njuma OJ, Ndontsa EN, Goodwin DC. Catalase in peroxidase clothing: interdependent cooperation of two cofactors in the catalytic versatility of KatG. Arch Biochem Biophys. 2014;544:27–39.CrossRefPubMedGoogle Scholar
  62. Ow SY, Dunstan DE. A brief overview of amyloids and Alzheimer’s disease. Protein Sci. 2014;23:1315–31.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Pastore A, Federici G, Bertini E, Piemonte F. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta. 2003;333:19–39.CrossRefPubMedGoogle Scholar
  64. Petrosillo G, Ruggiero FM, Paradies G. Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria. FASEB J. 2003;17:2202–8.CrossRefPubMedGoogle Scholar
  65. Podrez EA, Abu-Soud HM, Hazen SL. Myeloperoxidase-generated oxidants and atherosclerosis. Free Radic Biol Med. 2000;28:1717–25.CrossRefPubMedGoogle Scholar
  66. Pogocki D. Alzheimer’s beta-amyloid peptide as a source of neurotoxic free radicals: the role of structural effects. Acta Neurobiol Exp. 2003;63:131–45.Google Scholar
  67. Rajendran R, Minqin R, Ynsa MD, Casadesus G, Smith MA, Perry G, Halliwell B, et al. A novel approach to the identification and quantitative elemental analysis of amyloid deposits—insights into the pathology of Alzheimer’s disease. Biochem Biophys Res Commun. 2009;382:91–5.CrossRefPubMedGoogle Scholar
  68. Ridnour LA, Isenberg JS, Espey MG, Thomas DD, Roberts DD, Wink DA. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci U S A. 2005;102:13147–52.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52:581–7.CrossRefPubMedGoogle Scholar
  70. Robinson NC. Functional binding of cardiolipin to cytochrome-c-oxidase. J Bioenerg Biomembr. 1993;25:153–63.CrossRefPubMedGoogle Scholar
  71. Romero JC, Reckelhoff JF. State-of-the-art lecture. Role of angiotensin and oxidative stress in essential hypertension. Hypertension. 1999;34:943–9.CrossRefPubMedGoogle Scholar
  72. Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, Brownlee M, et al. Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol. 2005;289:F420–30.CrossRefPubMedGoogle Scholar
  73. Rossini AA, Like AA, Dulin WE, Cahill GF Jr. Pancreatic beta cell toxicity by streptozotocin anomers. Diabetes. 1977;26:1120–4.CrossRefPubMedGoogle Scholar
  74. Ruiz MC, Medina A, Moreno JM, Gómez I, Ruiz N, Bueno P, Asencio C, et al. Relationship between oxidative stress parameters and atherosclerotic signs in the carotid artery of stable renal transplant patients. Transplant Proc. 2005;37:3796–8.CrossRefPubMedGoogle Scholar
  75. Santucci R, Sinibaldi F, Polticelli F, Fiorucci L. Role of cardiolipin in mitochondrial diseases and apoptosis. Curr Med Chem. 2014;21:2702–14.CrossRefPubMedGoogle Scholar
  76. Semchyshyn HM, Miedzobrodzki J, Bayliak MM, Lozinska LM, Homza BV. Fructose compared with glucose is more a potent glycoxidation agent in vitro, but not under carbohydrate-induced stress in vivo: potential role of antioxidant and antiglycation enzymes. Carbohydr Res. 2014;384:61–9.CrossRefPubMedGoogle Scholar
  77. Sharma MK, Buettner GR. Interaction of vitamin C and vitamin E during free radical stress in plasma: an ESR study. Free Radic Biol Med. 1993;14:649–53.CrossRefPubMedGoogle Scholar
  78. Shearer J. Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics. Acc Chem Res. 2014;47:2332–41.CrossRefPubMedGoogle Scholar
  79. Shearer J, Long LM. A nickel superoxide dismutase maquette that reproduces the spectroscopic and functional properties of the metalloenzyme. Inorg Chem. 2006;45:2358–60.CrossRefPubMedGoogle Scholar
  80. Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr. 2015;6:64–72.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Sowers JR. Hypertension, angiotensin II, and oxidative stress. N Engl J Med. 2002;346:1999–2001.CrossRefPubMedGoogle Scholar
  82. Stein BW, Kirk ML. Electronic structure contributions to reactivity in xanthine oxidase family enzymes. J Biol Inorg Chem. 2015;20:183–94.CrossRefPubMedGoogle Scholar
  83. Stoyanovsky D, Murphy T, Anno PR, Kim YM, Salama G. Nitric oxide activates skeletal and cardiac ryanodine receptors. Cell Calcium. 1997;21:19–29.CrossRefPubMedGoogle Scholar
  84. Sultana R, Perluigi M, Allan Butterfield D. Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radic Biol Med. 2013;62:157–69.CrossRefPubMedGoogle Scholar
  85. Terao J. Dietary flavonoids as antioxidants. Forum Nutr. 2009;61:87–94.CrossRefPubMedGoogle Scholar
  86. Traverso N, Menini S, Odetti P, Pronzato MA, Cottalasso D, Marinari UM. Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver. Free Radic Biol Med. 2002;32:350–9.CrossRefPubMedGoogle Scholar
  87. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;266:37–56.CrossRefPubMedGoogle Scholar
  88. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.CrossRefPubMedGoogle Scholar
  89. VanderJagt DJ, Harrison JM, Ratliff DM, Hunsaker LA, Vander Jagt DL. Oxidative stress indices in IDDM subjects with and without long-term diabetic complications. Clin Biochem. 2001;34:265–70.CrossRefPubMedGoogle Scholar
  90. Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, Bursell S, et al. The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Invest. 2003;111:1373–80.CrossRefPubMedPubMedCentralGoogle Scholar
  91. Wang GG, XH L, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med. 2011:Article number 323171.Google Scholar
  92. Yuan XM, Li W. The iron hypothesis of atherosclerosis and its clinical impact. Ann Med. 2003;35:578–91.CrossRefPubMedGoogle Scholar
  93. Zhang Y, Zhao W, Zhang HJ, Domann FE, Oberley LW. Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. Cancer Res. 2002;62:1205–12.PubMedGoogle Scholar
  94. Zou MH, Shi CM, Cohen RA. Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J Clin Investig. 2002;109:817–26.CrossRefPubMedPubMedCentralGoogle Scholar
  95. Zucker IH, Schultz HD, Patel KP, Wang HJ. Modulation of angiotensin II signaling following exercise training in heart failure. Am J Physiol Heart Circ Physiol. 2015;308:H781–91.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Michael Lawson
    • 2
  • Klaudia Jomova
    • 2
  • Patrik Poprac
    • 1
  • Kamil Kuča
    • 3
    • 4
  • Kamil Musílek
    • 3
    • 4
  • Marian Valko
    • 1
    Email author
  1. 1.Faculty of Chemical and Food TechnologySlovak University of TechnologyBratislavaSlovakia
  2. 2.Department of Chemistry, Faculty of Natural SciencesConstantine the Philosopher UniversityNitraSlovakia
  3. 3.Biomedical Research CenterUniversity Hospital Hradec KraloveHradec KraloveCzech Republic
  4. 4.University of Hradec KraloveHradec KraloveCzech Republic

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