Sports Medicine

, Volume 46, Issue 5, pp 629–639 | Cite as

Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease

  • Erica N. Chirico
  • Camille Faës
  • Philippe Connes
  • Emmanuelle Canet-Soulas
  • Cyril Martin
  • Vincent Pialoux
Review Article


Sickle cell disease is a class of hemoglobinopathy in humans, which is the most common inherited disease in the world. Although complications of sickle cell disease start from polymerization of red blood cells during its deoxygenating phase, the oxidative stress resulting from the biological processes associated with this disease (ischaemic and hypoxic injuries, hemolysis and inflammation) has been shown to contribute to its pathophysiology. It is widely known that chronic exercise reduces oxidative stress in healthy people, mainly via improvement of antioxidant enzyme efficiency. In addition, recent studies in other diseases, as well as in sickle cell trait carriers and in a mouse model of sickle cell disease, have shown that regular physical activity could decrease oxidative stress. The purpose of this review is to summarize the role of oxidative stress in sickle cell disease and the effects of acute and chronic exercise on the pro-oxidant/antioxidant balance in sickle cell trait and sickle cell disease.


Nitric Oxide Exercise Training Sickle Cell Disease Xanthine Oxidase Sickle Cell Trait 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflicts of interest

Erica Chirico, Camille Faës, Philippe Connes, Emmanuelle Canet-Soulas, Cyril Martin and Vincent Pialoux declare that they have no conflicts of interest that are relevant to the content of this review.


No sources of funding were used in the preparation of this review.


  1. 1.
    Khan BV, Harrison DG, Olbrych MT, et al. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA. 1996;93:9114–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Akinsheye I, Klings ES. Sickle cell anemia and vascular dysfunction: the nitric oxide connection. J Cell Physiol. 2010;224:620–5. doi: 10.1002/jcp.22195.PubMedCrossRefGoogle Scholar
  3. 3.
    Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1005–28.PubMedGoogle Scholar
  4. 4.
    Chirico EN, Pialoux V. Role of oxidative stress in the pathogenesis of sickle cell disease. IUBMB Life. 2012;64:72–80. doi: 10.1002/iub.584.PubMedCrossRefGoogle Scholar
  5. 5.
    Nur E, Biemond BJ, Otten H-M, et al. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. Am J Hematol. 2011;86:484–9. doi: 10.1002/ajh.22012.PubMedCrossRefGoogle Scholar
  6. 6.
    Alsultan AI, Seif MA, Amin TT, et al. Relationship between oxidative stress, ferritin and insulin resistance in sickle cell disease. Eur Rev Med Pharmacol Sci. 2010;14:527–38.PubMedGoogle Scholar
  7. 7.
    El-Ghamrawy MK, Hanna WM, Abdel-Salam A, et al. Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study. J Pediatr (Rio J). 2014;90:286–92. doi: 10.1016/j.jped.2013.09.005.CrossRefGoogle Scholar
  8. 8.
    Gizi A, Papassotiriou I, Apostolakou F, et al. Assessment of oxidative stress in patients with sickle cell disease: the glutathione system and the oxidant-antioxidant status. Blood Cells Mol Dis. 2011;46:220–5. doi: 10.1016/j.bcmd.2011.01.002.PubMedCrossRefGoogle Scholar
  9. 9.
    Manfredini V, Lazzaretti LL, Griebeler IH, et al. Blood antioxidant parameters in sickle cell anemia patients in steady state. J Natl Med Assoc. 2008;100:897–902.PubMedCrossRefGoogle Scholar
  10. 10.
    Sultana C, Shen Y, Rattan V, et al. Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes. Blood. 1998;92:3924–35.PubMedGoogle Scholar
  11. 11.
    Torres LS, da Silva DG, Belini Junior E, et al. The influence of hydroxyurea on oxidative stress in sickle cell anemia. Rev Bras Hematol Hemoter. 2012;34:421–5. doi: 10.5581/1516-8484.20120106.PubMedCentralCrossRefGoogle Scholar
  12. 12.
    Oztas Y, Durukan I, Unal S, et al. Plasma protein oxidation is correlated positively with plasma iron levels and negatively with hemolysate zinc levels in sickle-cell anemia patients. Int J Lab Hematol. 2012;34:129–35. doi: 10.1111/j.1751-553X.2011.01369.x.PubMedCrossRefGoogle Scholar
  13. 13.
    Aslan M, Thornley-Brown D, Freeman BA. Reactive species in sickle cell disease. Ann N Y Acad Sci. 2000;899:375–91.PubMedCrossRefGoogle Scholar
  14. 14.
    Das SK, Nair RC. Superoxide dismutase, glutathione peroxidase, catalase and lipid peroxidation of normal and sickled erythrocytes. Br J Haematol. 1980;44:87–92.PubMedCrossRefGoogle Scholar
  15. 15.
    Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematol Am Soc Hematol Educ Program. 2008;1:177–83. doi: 10.1182/asheducation-2008.1.177.
  16. 16.
    Natta CL, Chen LC, Chow CK. Selenium and glutathione peroxidase levels in sickle cell anemia. Acta Haematol. 1990;83:130–2.PubMedCrossRefGoogle Scholar
  17. 17.
    Fasola F, Adedapo K, Anetor J, et al. Total antioxidants status and some hematological values in sickle cell disease patients in steady state. J Natl Med Assoc. 2007;99:891–4.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Dasgupta T, Hebbel RP, Kaul DK. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med. 2006;41:1771–80. doi: 10.1016/j.freeradbiomed.2006.08.025.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Schacter L, Warth JA, Gordon EM, et al. Altered amount and activity of superoxide dismutase in sickle cell anemia. FASEB J. 1988;2:237–43.PubMedGoogle Scholar
  20. 20.
    Amer J, Ghoti H, Rachmilewitz E, et al. Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br J Haematol. 2006;132:108–13. doi: 10.1111/j.1365-2141.2005.05834.x.PubMedCrossRefGoogle Scholar
  21. 21.
    Goswami K, Ray D. Putative pathogenic effect of oxidative stress in sickle cell disorder. Biomed Res. 2011;22:23–7.Google Scholar
  22. 22.
    Palazzetti S, Richard M-J, Favier A, et al. Overloaded training increases exercise-induced oxidative stress and damage. Can J Appl Physiol. 2003;28:588–604.PubMedCrossRefGoogle Scholar
  23. 23.
    Belini Junior E, da Silva DG, Torres LS, et al. Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time. Ann Hematol. 2012;91:479–89. doi: 10.1007/s00277-011-1340-y.PubMedCrossRefGoogle Scholar
  24. 24.
    Conran N, Franco-Penteado CF, Costa FF. Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin. 2009;33:1–16. doi: 10.1080/03630260802625709.PubMedCrossRefGoogle Scholar
  25. 25.
    Wood KC, Hsu LL, Gladwin MT. Sickle cell disease vasculopathy: a state of nitric oxide resistance. Free Radic Biol Med. 2008;44:1506–28. doi: 10.1016/j.freeradbiomed.2008.01.008.PubMedCrossRefGoogle Scholar
  26. 26.
    Hebbel RP, Morgan WT, Eaton JW, et al. Accelerated autoxidation and heme loss due to instability of sickle hemoglobin. Proc Natl Acad Sci USA. 1988;85:237–41.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Sheng K, Shariff M, Hebbel RP. Comparative oxidation of hemoglobins A and S. Blood. 1998;91:3467–70.PubMedGoogle Scholar
  28. 28.
    Hierso R, Waltz X, Mora P, et al. Effects of oxidative stress on red blood cell rheology in sickle cell patients. Br J Haematol. 2014;166:601–6. doi: 10.1111/bjh.12912.PubMedCrossRefGoogle Scholar
  29. 29.
    Belcher JD, Beckman JD, Balla G, et al. Heme degradation and vascular injury. Antioxid Redox Signal. 2010;12:233–48. doi: 10.1089/ars.2009.2822.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Kato GJ. Haptoglobin halts hemoglobin’s havoc. J Clin Invest. 2009;119:2140–2. doi: 10.1172/JCI40258.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Muller-Eberhard U, Javid J, Liem HH, et al. Plasma concentrations of hemopexin, haptoglobin and heme in patients with various hemolytic diseases. Blood. 1968;32:811–5.PubMedGoogle Scholar
  32. 32.
    Barodka VM, Nagababu E, Mohanty JG, et al. New insights provided by a comparison of impaired deformability with erythrocyte oxidative stress for sickle cell disease. Blood Cells Mol Dis. 2014;52:230–5. doi: 10.1016/j.bcmd.2013.10.004.PubMedCrossRefGoogle Scholar
  33. 33.
    Nagababu E, Gulyani S, Earley CJ, et al. Iron-deficiency anaemia enhances red blood cell oxidative stress. Free Radic Res. 2008;42:824–9. doi: 10.1080/10715760802459879.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Thomas SR, Witting PK, Drummond GR. Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2008;10:1713–65. doi: 10.1089/ars.2008.2027.PubMedCrossRefGoogle Scholar
  35. 35.
    Grau M, Mozar A, Charlot K, et al. High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia. Br J Haematol. 2015;168:728–36. doi: 10.1111/bjh.13185.PubMedCrossRefGoogle Scholar
  36. 36.
    Reiter CD, Gladwin MT. An emerging role for nitric oxide in sickle cell disease vascular homeostasis and therapy. Curr Opin Hematol. 2003;10:99–107.PubMedCrossRefGoogle Scholar
  37. 37.
    Morris CR, Kuypers FA, Larkin S, et al. Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. Br J Haematol. 2000;111:498–500.PubMedCrossRefGoogle Scholar
  38. 38.
    Jeffers A, Gladwin MT, Kim-Shapiro DB. Computation of plasma hemoglobin nitric oxide scavenging in hemolytic anemias. Free Radic Biol Med. 2006;41:1557–65. doi: 10.1016/j.freeradbiomed.2006.08.017.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005;294:81–90. doi: 10.1001/jama.294.1.81.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Gladwin MT, Schechter AN, Ognibene FP, et al. Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation. 2003;107:271–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Wood KC, Hebbel RP, Lefer DJ, et al. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med. 2006;40:1443–53. doi: 10.1016/j.freeradbiomed.2005.12.015.PubMedCrossRefGoogle Scholar
  42. 42.
    Vilas-Boas W, Cerqueira BAV, Zanette AMD, et al. Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients. Ann Hematol. 2010;89:877–82. doi: 10.1007/s00277-010-0954-9.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kaul DK, Zhang X, Dasgupta T, et al. Arginine therapy of transgenic-knockout sickle mice improves microvascular function by reducing non-nitric oxide vasodilators, hemolysis, and oxidative stress. Am J Physiol Heart Circ Physiol. 2008;295:H39–47. doi: 10.1152/ajpheart.00162.2008.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Cosentino F, Hürlimann D, Delli Gatti C, et al. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia. Heart. 2008;94:487–92. doi: 10.1136/hrt.2007.122184.PubMedCrossRefGoogle Scholar
  45. 45.
    Uzunova VV, Pan W, Galkin O, et al. Free heme and the polymerization of sickle cell hemoglobin. Biophys J. 2010;99:1976–85. doi: 10.1016/j.bpj.2010.07.024.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Bunn HF, Noguchi CT, Hofrichter J, et al. Molecular and cellular pathogenesis of hemoglobin SC disease. Proc Natl Acad Sci USA. 1982;79:7527–31.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Szocs K. Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen Physiol Biophys. 2004;23:265–95.PubMedGoogle Scholar
  48. 48.
    Osarogiagbon UR, Choong S, Belcher JD, et al. Reperfusion injury pathophysiology in sickle transgenic mice. Blood. 2000;96:314–20.PubMedGoogle Scholar
  49. 49.
    Mahaseth H, Vercellotti GM, Welch TE, et al. Polynitroxyl albumin inhibits inflammation and vasoocclusion in transgenic sickle mice. J Lab Clin Med. 2005;145:204–11.PubMedCrossRefGoogle Scholar
  50. 50.
    Sen CK. Oxidants and antioxidants in exercise. J Appl Physiol. 1995;79:675–86.PubMedGoogle Scholar
  51. 51.
    Leeuwenburgh C, Heinecke JW. Oxidative stress and antioxidants in exercise. Curr Med Chem. 2001;8:829–38.PubMedCrossRefGoogle Scholar
  52. 52.
    Gomes EC, Silva AN, de Oliveira MR. Oxidants, antioxidants, and the beneficial roles of exercise-induced production of reactive species. Oxid Med Cell Longev. 2012;2012:756132. doi: 10.1155/2012/756132.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Davies KJ, Quintanilha AT, Brooks GA, et al. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun. 1982;107:1198–205.PubMedCrossRefGoogle Scholar
  54. 54.
    Ashton T, Rowlands CC, Jones E, et al. Electron spin resonance spectroscopic detection of oxygen-centred radicals in human serum following exhaustive exercise. Eur J Appl Physiol Occup Physiol. 1998;77:498–502.PubMedCrossRefGoogle Scholar
  55. 55.
    Faes C, Martin C, Chirico EN, et al. Effect of sickle cell trait and/or alpha thalassemia on exercise-induced oxidative stress. Acta Physiol. 2012;205:541–50.Google Scholar
  56. 56.
    Bailey DM, Young IS, McEneny J, et al. Regulation of free radical outflow from an isolated muscle bed in exercising humans. Am J Physiol Heart Circ Physiol. 2004;287:H1689–99. doi: 10.1152/ajpheart.00148.2004.PubMedCrossRefGoogle Scholar
  57. 57.
    Dillard CJ, Litov RE, Savin WM, et al. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation. J Appl Physiol. 1978;45:927–32.PubMedGoogle Scholar
  58. 58.
    Jackson MJ, Edwards RH, Symons MC. Electron spin resonance studies of intact mammalian skeletal muscle. Biochim Biophys Acta. 1985;847:185–90.PubMedCrossRefGoogle Scholar
  59. 59.
    Groussard C, Rannou-Bekono F, Machefer G, et al. Changes in blood lipid peroxidation markers and antioxidants after a single sprint anaerobic exercise. Eur J Appl Physiol. 2003;89:14–20. doi: 10.1007/s00421-002-0767-1.PubMedCrossRefGoogle Scholar
  60. 60.
    Goto C, Higashi Y, Kimura M, et al. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation. 2003;108:530–5. doi: 10.1161/01.CIR.0000080893.55729.28.PubMedCrossRefGoogle Scholar
  61. 61.
    Goto C, Nishioka K, Umemura T, et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens. 2007;20:825–30. doi: 10.1016/j.amjhyper.2007.02.014.PubMedCrossRefGoogle Scholar
  62. 62.
    Bloomer RJ, Davis PG, Consitt LA, et al. Plasma protein carbonyl response to increasing exercise duration in aerobically trained men and women. Int J Sports Med. 2007;28:21–5. doi: 10.1055/s-2006-924140.PubMedCrossRefGoogle Scholar
  63. 63.
    Fatouros IG, Jamurtas AZ, Villiotou V, et al. Oxidative stress responses in older men during endurance training and detraining. Med Sci Sports Exerc. 2004;36:2065–72.PubMedCrossRefGoogle Scholar
  64. 64.
    Robertson JD, Maughan RJ, Duthie GG, et al. Increased blood antioxidant systems of runners in response to training load. Clin Sci. 1991;80:611–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Pialoux V, Brown AD, Leigh R, et al. Effect of cardiorespiratory fitness on vascular regulation and oxidative stress in postmenopausal women. Hypertension. 2009;54:1014–20. doi: 10.1161/HYPERTENSIONAHA.109.138917.PubMedCrossRefGoogle Scholar
  66. 66.
    Steinberg JG, Delliaux S, Jammes Y. Reliability of different blood indices to explore the oxidative stress in response to maximal cycling and static exercises. Clin Physiol Funct Imaging. 2006;26:106–12. doi: 10.1111/j.1475-097X.2006.00658.x.PubMedCrossRefGoogle Scholar
  67. 67.
    Watson TA, Callister R, Taylor RD, et al. Antioxidant restriction and oxidative stress in short-duration exhaustive exercise. Med Sci Sports Exerc. 2005;37:63–71.PubMedCrossRefGoogle Scholar
  68. 68.
    Michailidis Y, Jamurtas AZ, Nikolaidis MG, et al. Sampling time is crucial for measurement of aerobic exercise-induced oxidative stress. Med Sci Sports Exerc. 2007;39:1107–13. doi: 10.1249/01.mss.0b013e318053e7ba.PubMedCrossRefGoogle Scholar
  69. 69.
    Alessio HM, Hagerman AE, Fulkerson BK, et al. Generation of reactive oxygen species after exhaustive aerobic and isometric exercise. Med Sci Sports Exerc. 2000;32:1576–81.PubMedCrossRefGoogle Scholar
  70. 70.
    Bloomer RJ, Fisher-Wellman KH. Blood oxidative stress biomarkers: influence of sex, exercise training status, and dietary intake. Gend Med. 2008;5:218–28. doi: 10.1016/j.genm.2008.07.002.PubMedCrossRefGoogle Scholar
  71. 71.
    Radak Z, Chung HY, Goto S. Systemic adaptation to oxidative challenge induced by regular exercise. Free Radic Biol Med. 2008;44:153–9. doi: 10.1016/j.freeradbiomed.2007.01.029.PubMedCrossRefGoogle Scholar
  72. 72.
    Miyazaki H, Oh-ishi S, Ookawara T, et al. Strenuous endurance training in humans reduces oxidative stress following exhausting exercise. Eur J Appl Physiol. 2001;84:1–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Liu J, Yeo HC, Övervik-Douki E, et al. Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol. 2000;89:21–8.PubMedGoogle Scholar
  74. 74.
    Leeuwenburgh C, Fiebig R, Chandwaney R, et al. Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. Am J Physiol. 1994;267:R439–45.PubMedGoogle Scholar
  75. 75.
    Powers SK, Criswell D, Lawler J, et al. Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle. Am J Physiol. 1994;266:R375–80.PubMedGoogle Scholar
  76. 76.
    Oh-ishi S, Kizaki T, Nagasawa J, et al. Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle. Clin Exp Pharmacol Physiol. 1997;24:326–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Laughlin MH, Simpson T, Sexton WL, et al. Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training. J Appl Physiol. 1990;68:2337–43.PubMedGoogle Scholar
  78. 78.
    Ji LL. Exercise and oxidative stress: role of the cellular antioxidant systems. Exerc Sport Sci Rev. 1995;23:135–66.PubMedCrossRefGoogle Scholar
  79. 79.
    Leeuwenburgh C, Ji LL. Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. Arch Biochem Biophys. 1995;316:941–9. doi: 10.1006/abbi.1995.1125.PubMedCrossRefGoogle Scholar
  80. 80.
    Aikawa KM, Quintanilha AT, de Lumen BO, et al. Exercise endurance-training alters vitamin E tissue levels and red-blood-cell hemolysis in rodents. Biosci Rep. 1984;4:253–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Paik I-Y, Jeong M-H, Jin H-E, et al. Fluid replacement following dehydration reduces oxidative stress during recovery. Biochem Biophys Res Commun. 2009;383:103–7. doi: 10.1016/j.bbrc.2009.03.135.PubMedCrossRefGoogle Scholar
  82. 82.
    Hillman AR, Vince RV, Taylor L, et al. Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress. Appl Physiol Nutr Metab. 2011;36:698–706. doi: 10.1139/h11-080.PubMedCrossRefGoogle Scholar
  83. 83.
    Kellum JA, Song M, Li J. Science review: extracellular acidosis and the immune response: clinical and physiologic implications. Crit Care. 2004;8:331–6. doi: 10.1186/cc2900.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Pialoux V, Mounier R, Brown AD, et al. Relationship between oxidative stress and HIF-1 alpha mRNA during sustained hypoxia in humans. Free Radic Biol Med. 2009;46:321–6. doi: 10.1016/j.freeradbiomed.2008.10.047.PubMedCrossRefGoogle Scholar
  85. 85.
    Powers SK, Nelson WB, Hudson MB. Exercise-induced oxidative stress in humans: cause and consequences. Free Radic Biol Med. 2011;51:942–50. doi: 10.1016/j.freeradbiomed.2010.12.009.PubMedCrossRefGoogle Scholar
  86. 86.
    Newcomer SC, Thijssen DHJ, Green DJ. Effects of exercise on endothelium and endothelium/smooth muscle cross talk: role of exercise-induced hemodynamics. J Appl Physiol. 2011;111:311–20. doi: 10.1152/japplphysiol.00033.2011.PubMedCrossRefGoogle Scholar
  87. 87.
    Connes P, Machado R, Hue O, et al. Exercise limitation, exercise testing and exercise recommendations in sickle cell anemia. Clin Hemorheol Microcirc. 2011;49:151–63. doi: 10.3233/CH-2011-1465.PubMedGoogle Scholar
  88. 88.
    Le Gallais D, Lonsdorfer J, Bogui P, et al. Point:counterpoint: sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity. J Appl Physiol. 2007;103:2137–8. doi: 10.1152/japplphysiol.00338.2007.PubMedCrossRefGoogle Scholar
  89. 89.
    Connes P, Hardy-Dessources M-D, Hue O. Counterpoint: sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity. J Appl Physiol. 2007;103:2138–40. doi: 10.1152/japplphysiol.00338.2007a.PubMedCrossRefGoogle Scholar
  90. 90.
    Kark JA, Ward FT. Exercise and hemoglobin S. Semin Hematol. 1994;31:181–225.PubMedGoogle Scholar
  91. 91.
    Connes P, Harmon KG, Bergeron MF. Pathophysiology of exertional death associated with sickle cell trait: can we make a parallel with vaso-occlusion mechanisms in sickle cell disease? Br J Sports Med. 2013;47:190. doi: 10.1136/bjsports-2012-091223.PubMedCrossRefGoogle Scholar
  92. 92.
    Eichner ER. Sickle cell trait in sports. Curr Sports Med Rep. 2010;9:347–51. doi: 10.1249/JSR.0b013e3181fc73d7.PubMedCrossRefGoogle Scholar
  93. 93.
    Kark JA, Posey DM, Schumacher HR, et al. Sickle-cell trait as a risk factor for sudden death in physical training. N Engl J Med. 1987;317:781–7. doi: 10.1056/NEJM198709243171301.PubMedCrossRefGoogle Scholar
  94. 94.
    Kerle KK, Nishimura KD. Exertional collapse and sudden death associated with sickle cell trait. Mil Med. 1996;161:766–7.PubMedGoogle Scholar
  95. 95.
    Ferster K, Eichner ER. Exertional sickling deaths in Army recruits with sickle cell trait. Mil Med. 2012;177:56–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Harmon KG, Drezner JA, Klossner D, et al. Sickle cell trait associated with a RR of death of 37 times in National Collegiate Athletic Association football athletes: a database with 2 million athlete-years as the denominator. Br J Sports Med. 2012;46:325–30. doi: 10.1136/bjsports-2011-090896.PubMedCrossRefGoogle Scholar
  97. 97.
    Kuypers FA, Marsh AM. Research in athletes with sickle cell trait: just do it. J Appl Physiol. 2012;112:1433. doi: 10.1152/japplphysiol.00221.2012.PubMedCrossRefGoogle Scholar
  98. 98.
    Hebbel RP, Eaton JW, Balasingam M, et al. Spontaneous oxygen radical generation by sickle erythrocytes. J Clin Invest. 1982;70:1253–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Connes P, Reid H, Hardy-Dessources M-D, et al. Physiological responses of sickle cell trait carriers during exercise. Sports Med. 2008;38:931–46.PubMedCrossRefGoogle Scholar
  100. 100.
    Tripette J, Connes P, Beltan E, et al. Red blood cell deformability and aggregation, cell adhesion molecules, oxidative stress and nitric oxide markers after a short term, submaximal, exercise in sickle cell trait carriers. Clin Hemorheol Microcirc. 2010;45:39–52. doi: 10.3233/CH-2010-1325.PubMedGoogle Scholar
  101. 101.
    Das SK, Hinds JE, Hardy RE, et al. Effects of physical stress on peroxide scavengers in normal and sickle cell trait erythrocytes. Free Radic Biol Med. 1993;14:139–47.PubMedCrossRefGoogle Scholar
  102. 102.
    Faës C, Martin C, Chirico EN, et al. Effect of α-thalassaemia on exercise-induced oxidative stress in sickle cell trait. Acta Physiol (Oxf). 2012;205:541–50. doi: 10.1111/j.1748-1716.2012.02434.x.CrossRefGoogle Scholar
  103. 103.
    Sen CK. Antioxidants in exercise nutrition. Sports Med. 2001;31:891–908.PubMedCrossRefGoogle Scholar
  104. 104.
    Bloomer RJ. Effect of exercise on oxidative stress biomarkers. Adv Clin Chem. 2008;46:1–50.PubMedCrossRefGoogle Scholar
  105. 105.
    Pialoux V, Mounier R, Ponsot E, et al. Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance. Eur J Clin Nutr. 2006;60:1345–54. doi: 10.1038/sj.ejcn.1602462.PubMedCrossRefGoogle Scholar
  106. 106.
    Aufradet E, Monchanin G, Oyonno-Engelle S, et al. Habitual physical activity and endothelial activation in sickle cell trait carriers. Med Sci Sports Exerc. 2010;42:1987–94. doi: 10.1249/MSS.0b013e3181e054d6.PubMedCrossRefGoogle Scholar
  107. 107.
    Vincent L, Oyono-Enguéllé S, Féasson L, et al. Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell trait. J Appl Physiol. 2012;113:549–56. doi: 10.1152/japplphysiol.01573.2011.PubMedCrossRefGoogle Scholar
  108. 108.
    Chirico EN, Martin C, Faës C, et al. Exercise training blunts oxidative stress in sickle cell trait carriers. J Appl Physiol. 2012;112:1445–53. doi: 10.1152/japplphysiol.01452.2011.PubMedCrossRefGoogle Scholar
  109. 109.
    Moheeb H, Wali YA, El-Sayed MS. Physical fitness indices and anthropometrics profiles in schoolchildren with sickle cell trait/disease. Am J Hematol. 2007;82:91–7. doi: 10.1002/ajh.20755.PubMedCrossRefGoogle Scholar
  110. 110.
    Barbeau P, Woods KF, Ramsey LT, et al. Exercise in sickle cell anemia: effect on inflammatory and vasoactive mediators. Endothelium. 2001;8:147–55.PubMedCrossRefGoogle Scholar
  111. 111.
    Faës C, Balayssac-Siransy E, Connes P, et al. Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation. Br J Haematol. 2014;164:124–30. doi: 10.1111/bjh.12594.PubMedCrossRefGoogle Scholar
  112. 112.
    Balayssac-Siransy E, Connes P, Tuo N, et al. Mild haemorheological changes induced by a moderate endurance exercise in patients with sickle cell anaemia. Br J Haematol. 2011;154:398–407. doi: 10.1111/j.1365-2141.2011.08728.x.PubMedCrossRefGoogle Scholar
  113. 113.
    Waltz X, Hedreville M, Sinnapah S, et al. Delayed beneficial effect of acute exercise on red blood cell aggregate strength in patients with sickle cell anemia. Clin Hemorheol Microcirc. 2012;52(1):15–26. doi: 10.3233/CH-2012-1540.PubMedGoogle Scholar
  114. 114.
    Aufradet E, Douillard A, Charrin E, et al. Physical activity limits pulmonary endothelial activation in sickle cell SAD mice. Blood. 2014;123:2745–7. doi: 10.1182/blood-2013-10-534982.PubMedCrossRefGoogle Scholar
  115. 115.
    Charrin E, Aufradet E, Douillard A, et al. Oxidative stress is decreased in physically active sickle cell SAD mice. Br J Haematol. 2015;168:747–56. doi: 10.1111/bjh.13207.PubMedCrossRefGoogle Scholar
  116. 116.
    Cocks M, Shaw CS, Shepherd SO, et al. Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males. J Physiol (Lond). 2013;591:641–56. doi: 10.1113/jphysiol.2012.239566.PubMedCentralCrossRefGoogle Scholar
  117. 117.
    Covas M-I, Elosua R, Fitó M, et al. Relationship between physical activity and oxidative stress biomarkers in women. Med Sci Sports Exerc. 2002;34:814–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Alcorn R, Bowser B, Henley EJ, et al. Fluidotherapy and exercise in the management of sickle cell anemia: a clinical report. Phys Ther. 1984;64:1520–2.PubMedGoogle Scholar
  119. 119.
    Tinti G, Somera R Jr, Valente FM, et al. Benefits of kinesiotherapy and aquatic rehabilitation on sickle cell anemia: a case report. Genet Mol Res. 2010;9:360–4. doi: 10.4238/vol9-1gmr722.PubMedCrossRefGoogle Scholar
  120. 120.
    Zanoni CT, Galvão F, Cliquet Junior A, et al. Pilot randomized controlled trial to evaluate the effect of aquatic and land physical therapy on musculoskeletal dysfunction of sickle cell disease patients. Rev Bras Hematol Hemoter. 2015;37:82–9. doi: 10.1016/j.bjhh.2014.11.010.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Erica N. Chirico
    • 1
    • 2
  • Camille Faës
    • 1
    • 3
  • Philippe Connes
    • 1
    • 3
    • 4
  • Emmanuelle Canet-Soulas
    • 2
  • Cyril Martin
    • 1
    • 3
  • Vincent Pialoux
    • 1
    • 3
    • 4
  1. 1.EA 647 Centre de Recherche et d’Innovation sur le SportUniversité Claude Bernard Lyon 1, Université de LyonVilleurbanneFrance
  2. 2.Cardiovascular, Metabolism, Diabetes, and Nutrition (CarMeN INSERM U-1060), Faculty of Medicine Lyon SudUniversité Claude Bernard Lyon 1OullinsFrance
  3. 3.Laboratory of Excellence in Red Blood Cell (LABEX GR-Ex)PRES SorbonneParisFrance
  4. 4.Institut Universitaire de FranceParisFrance

Personalised recommendations