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The Journal of Critical Care Medicine

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Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury

Loredana Luca / Alexandru Florin Rogobete
  • Clinic of Anaesthesia and Intensive Care, Emergency County Hospital ”Pius Brînzeu”, Timişoara, Romania
  • Faculty of Medicine, ”Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania
  • Faculty of Chemistry, Biology, Geography, West University of Timişoara, Timişoara, Romania
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/ Ovidiu Horea Bedreag
  • Corresponding author
  • Clinic of Anaesthesia and Intensive Care, Emergency County Hospital ”Pius Brînzeu”, Timişoara, Romania
  • Faculty of Medicine, ”Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania
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Published Online: 2015-08-06 | DOI: https://doi.org/10.1515/jccm-2015-0014

Abstract

Traumatic Brain Injury (TBI) is one of the leading causes of death among critically ill patients from the Intensive Care Units (ICU). After primary traumatic injuries, secondary complications occur, which are responsible for the progressive degradation of the clinical status in this type of patients. These include severe inflammation, biochemical and physiological imbalances and disruption of the cellular functionality. The redox cellular potential is determined by the oxidant/antioxidant ratio. Redox potential is disturbed in case of TBI leading to oxidative stress (OS). A series of agression factors that accumulate after primary traumatic injuries lead to secondary lesions represented by brain ischemia and hypoxia, inflammatory and metabolic factors, coagulopathy, microvascular damage, neurotransmitter accumulation, blood-brain barrier disruption, excitotoxic damage, blood-spinal cord barrier damage, and mitochondrial dysfunctions. A cascade of pathophysiological events lead to accelerated production of free radicals (FR) that further sustain the OS. To minimize the OS and restore normal oxidant/antioxidant ratio, a series of antioxidant substances is recommended to be administrated (vitamin C, vitamin E, resveratrol, N-acetylcysteine). In this paper we present the biochemical and pathophysiological mechanism of action of FR in patients with TBI and the antioxidant therapy available.

Keywords: antioxidant therapy; oxidative stress; traumatic brain injury; multiple trauma patients

References

  • 1. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta - Mol Basis Dis. 2012;1822:675–84.Google Scholar

  • 2. Humberto J, Mantilla M, Fernando L, Arboleda G. Revista Colombiana de Anestesiología Anesthesia for patients with traumatic brain injury. Colomb J Anesthesiol. 2015;43:3–8.Google Scholar

  • 3. Ashafaq M, Varshney L, Khan MHA, et al. Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes. Biomed Res Int. 2014;2014: 249031.Google Scholar

  • 4. Sies H. Redox Biology Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180–3.CrossrefPubMedGoogle Scholar

  • 5. Ribeiro A, Ferraz-de-Paula V, Pinheiro ML, et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A2A receptor. Eur J Pharmacol. 2012;678:78–85.Google Scholar

  • 6. Abdul-Muneer PM, Chandra N, Haorah J. Interactions of Oxidative Stress and Neurovascular Inflammation in the Pathogenesis of Traumatic Brain Injury. Mol Neurobiol. 2015;51:966-79CrossrefGoogle Scholar

  • 7. Bibi H, Vinokur V, Waisman D, et al. Zn/Ga-DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma. Redox Biol. 2014;2:814–9.CrossrefGoogle Scholar

  • 8. Hall ED, Vaishnav R a., Mustafa AG. Antioxidant Therapies for Traumatic Brain Injury. Neurotherapeutics. 2010;7:51–61.CrossrefPubMedGoogle Scholar

  • 9. Miller DM, Singh IN, Wang JA, Hall ED. Nrf2 – ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice. Exp Neurol. 2015;264:103–10.Google Scholar

  • 10. Rodríguez-Rodríguez A, Egea-Guerrero JJ, León-Justel A, et al. Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults. Clin Chim Acta. 2012;414:228–33.Google Scholar

  • 11. Strathmann FG, Schulte S, Goerl K, Petron DJ. Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin Biochem. 2014;47:876–88.PubMedCrossrefGoogle Scholar

  • 12. Kumar RG, Diamond ML, Boles JA, et al. Acute CSF interleukin-6 trajectories after TBI: Associations with neuroinflammation, polytrauma, and outcome. Brain Behav Immun. 2014;45:253–62.PubMedCrossrefGoogle Scholar

  • 13. Falcone T, Janigro D, Lovell R, et al. S100B blood levels and childhood trauma in adolescent inpatients. J Psychiatr Res. 2014;62:14–22.Google Scholar

  • 14. Cervellin G, Benatti M, Carbucicchio A, et al. Serum levels of protein S100B predict intracranial lesions in mild head injury. Clin Biochem. 2012;45:408–11.CrossrefGoogle Scholar

  • 15. Dal-Pizzol F, Ritter C, Cassol-Jr OJ, et al. Oxidative mechanisms of brain dysfunction during sepsis. Neurochem Res. 2010;35:1–12.CrossrefGoogle Scholar

  • 16. Hol EM, Pekny M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol. 2015;32C:121–30.CrossrefPubMedGoogle Scholar

  • 17. Feneberg E, Steinacker P, Lehnert S, Böhm B, Mayer G, Otto M. Elevated glial fibrillary acidic protein levels in the cerebrospinal fluid of patients with narcolepsy. Sleep Med. 2013;14:692–4.CrossrefPubMedGoogle Scholar

  • 18. Tennakoon AH, Izawa T, Wijesundera KK, et al. Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA). Exp Toxicol Pathol. 2015;67:53–63.CrossrefGoogle Scholar

  • 19. Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie L. Serum microRNA signatures identified by Solexa sequencing predict sepsis patients’ mortality: A prospective observational study. PLoS One. 2012;7:1–9.Google Scholar

  • 20. Abdul-Muneer PM, Schuetz H, Wang F, et al. Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast. Free Radic Biol Med. 2013;60:282–91.Google Scholar

  • 21. Petzold A. Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. Brain Res. 2014;1600:17–31.Google Scholar

  • 22. Kärkelä J, Bock E, Kaukinen S. CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. J Neurol Sci. 1993;116:100–9.CrossrefPubMedGoogle Scholar

  • 23. Prasad KN, Bondy SC. Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI. Brain Res. 2015;1599:103–14.Google Scholar

  • 24. El-Maraghi S, Yehia H, Hossam H, Yehia A, Mowafy H. The prognostic value of neuron specific enolase in head injury. Egypt J Crit Care Med. 2013;1:25–32.Google Scholar

  • 25. Klevay LM. Myelin and traumatic brain injury: the copper deficiency hypothesis. Med Hypotheses. 2013;81:995–8.PubMedCrossrefGoogle Scholar

  • 26. Barco S, Gennai I, Reggiardo G, et al. Urinary homovanillic and vanillylmandelic acid in the diagnosis of neuroblastoma: report from the Italian Cooperative Group for Neuroblastoma. Clin Biochem. 2014;47:848–52.CrossrefGoogle Scholar

  • 27. Dash PK, Zhao J, Hergenroeder G, Moore AN. Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics. 2010;7:100–14.CrossrefPubMedGoogle Scholar

  • 28. LeWitt P, Schultz L, Auinger P, Lu M. CSF xanthine, homovanillic acid, and their ratio as biomarkers of Parkinson’s disease. Brain Res. 2011;1408:88–97.Google Scholar

  • 29. Homsi S, Federico F, Croci N, et al. Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res. 2009;1291:122–32.Google Scholar

  • 30. Zampieri FG, Kellum J A, Park M, et al. Relationship between acid-base status and inflammation in the critically ill. Crit Care. 2014;18:R154.CrossrefGoogle Scholar

  • 31. Ansari M a., Roberts KN, Scheff SW. Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radic Biol Med. 2008;45:443–52.Google Scholar

  • 32. Wannhoff A, Bölck B, Kübler AC, Bloch W, Reuther T. Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo[a]pyrene. Toxicol In Vitro. 2013;27:915–21.PubMedCrossrefGoogle Scholar

  • 33. Hohl A, Gullo JDS, Silva CCP, et al. Plasma levels of oxidative stress biomarkers and hospital mortality in severe head injury: A multivariate analysis. J Crit Care. 2012;27:523.e11–523.e19.CrossrefPubMedGoogle Scholar

  • 34. Ji H-H, Huang G-L, Yin H-X, Xu P, Luo S-Y, Song J-K. Association between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphisms and esophageal cancer risk: A meta-analysis. Meta Gene. 2015;3:14–25.Google Scholar

  • 35. Muraoka T, Soh J, Toyooka S, et al. The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma. Lung Cancer. 2013;82:485–90.Google Scholar

  • 36. Li Y, Dalli J, Chiang N, Baron RM, Quintana C, Serhan CN. Plasticity of leukocytic exudates in resolving acute inflammation is regulated by MicroRNA and proresolving mediators. Immunity. 2013;39:885–98.PubMedCrossrefGoogle Scholar

  • 37. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P. Alterations in microRNA expression in stress-induced cellular senescence. Mech Ageing Dev. 2009;130:731–41.Google Scholar

  • 38. Suh JH, Choi E, Cha M-J, et al. Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal cardiomyocytes by repressing GSK-3β protein expression. Biochem Biophys Res Commun. 2012;423:404–10.Google Scholar

  • 39. Miller A-F. Superoxide dismutases: ancient enzymes and new insights. FEBS Lett. 2012;586:585–95.Google Scholar

  • 40. Gerbaud P, Petzold L, Thérond P, Anderson WB, Evain-Brion D, Raynaud F. Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid in normal and psoriatic human fibroblasts. J Autoimmun. 2005;24:69–78.PubMedCrossrefGoogle Scholar

  • 41. Pilon M, Ravet K, Tapken W. The biogenesis and physiological function of chloroplast superoxide dismutases. Biochim Biophys Acta. 2011;1807:989–98.Google Scholar

  • 42. Comar JF, Babeto De Sá-Nakanishi A, De Oliveira AL, et al. Oxidative state of the liver of rats with adjuvant-induced arthritis. Free Radic Biol Med. 2013;58:144–53.Google Scholar

  • 43. Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28:219–42.CrossrefPubMedGoogle Scholar

  • 44. Lazzarino G, Di Pietro V, Lazzarino G, et al. Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat. Free Radic Biol Med. 2014;69:258–64.Google Scholar

  • 45. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32:234–46.CrossrefGoogle Scholar

  • 46. Elkharaz J, Ugun-Klusek A, Constantin-Teodosiu D, et al. Implications for oxidative stress and astrocytes following 26S proteasomal depletion in mouse forebrain neurones. Biochim Biophys Acta - Mol Basis Dis. 2013;1832:1959–68.Google Scholar

  • 47. Li L, Zhu K, Liu Y, et al. Targeting Thioredoxin-1 With Sirna Exacerbates Oxidative Stress Injury After Cerebral Ischemia / Reperfusion in Rats. 2015;284:815–23.Google Scholar

  • 48. Andrés NC, Fermento ME, Gandini NA, et al. Heme oxygenase-1 has antitumoral effects in colorectal cancer: involvement of p53. Exp Mol Pathol. 2014;97:321–31.CrossrefGoogle Scholar

  • 49. Yu JH, Cho SO, Lim JW, Kim N, Kim H. Ataxia telangiectasia mutated inhibits oxidative stress-induced apoptosis by regulating heme oxygenase-1 expression. Int J Biochem Cell Biol. 2015;60:147–56.PubMedCrossrefGoogle Scholar

  • 50. Namba F, Go H, Murphy J A., et al. Expression level and subcellular localization of heme oxygenase-1 modulates its cytoprotective properties in response to lung injury: A mouse model. PLoS One. 2014;9:1–11.CrossrefGoogle Scholar

  • 51. Kurtz P, Claassen J, Helbok R, et al. Systemic glucose variability predicts cerebral metabolic distress and mortality after subarachnoid hemorrhage: a retrospective observational study. Crit Care. 2014;18:R89.PubMedCrossrefGoogle Scholar

  • 52. Beschorner R, Adjodah D, Schwab JM, et al. Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol. 2000;100:377–84.CrossrefPubMedGoogle Scholar

  • 53. Bhalla P, Dhawan DK. Protective Role of Lithium in Ameliorating the Aluminium-induced Oxidative Stress and Histological Changes in Rat Brain. Cell Mol Neurobiol. 2009;29:513–21.PubMedCrossrefGoogle Scholar

  • 54. Blass SC, Goost H, Tolba RH, et al. Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: A PRCT. Clin Nutr. 2012;31:469–75.PubMedCrossrefGoogle Scholar

  • 55. Şener G, Toklu H, Kapucu C, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today. 2005;35:52–9.CrossrefGoogle Scholar

  • 56. Dehghan F, Khaksari Hadad M, Asadikram G, Najafipour H, Shahrokhi N. Effect of melatonin on intracranial pressure and brain edema following traumatic brain injury: Role of oxidative stresses. Arch Med Res. 2013;44:251–8.PubMedCrossrefGoogle Scholar

  • 57. Yürüker V, Naz M, Nilgün Ş. Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: Possible involvement of TRPM2 channels. Metab Brain Dis. 2015;30:223–31.CrossrefGoogle Scholar

  • 58. Bhalla a., Singhal M, Suri V, Malhotra S, Shafiq N, Varma S. Methylprednisolone in dengue patients with alarm signs: The MIDWAS study. Int J Infect Dis. 2014;21:323.Google Scholar

  • 59. Grasbon-Frodl EM, Nakao N, Brundin P. The lazaroid U-83836E improves the survival of rat embryonic mesencephalic tissue stored at 4°C and subsequently used for cultures or intracerebral transplantation. Brain Res Bull. 1996;39:341–7.CrossrefGoogle Scholar

  • 60. Porfire AS, Leucuţa SE, Kiss B, Loghin F, Pârvu AE. Investigation into the role of Cu/Zn-SOD delivery system on its antioxidant and antiinflammatory activity in rat model of peritonitis. Pharmacol Reports. 2014;66:670–6.CrossrefGoogle Scholar

  • 61. Schmatz R, Perreira LB, Stefanello N, et al. Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie. 2012;94:374–83.PubMedCrossrefGoogle Scholar

  • 62. Koz ST, Etem EO, Baydas G, et al. Effects of resveratrol on blood homocysteine level, on homocysteine induced oxidative stress, apoptosis and cognitive dysfunctions in rats. Brain Res. 2012;1484:29–38.Google Scholar

  • 63. Song L, Chen L, Zhang X, Li J, Le W. Resveratrol Ameliorates Motor Neuron Degeneration and Improves Survival in SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis. Biomed Res Int. 2014;2014:483501.Google Scholar

  • 64. Gao J, Koshio S, Ishikawa M, Yokoyama S, Mamauag REP. Interactive effects of vitamin C and E supplementation on growth performance, fatty acid composition and reduction of oxidative stress in juvenile Japanese flounder Paralichthys olivaceus fed dietary oxidized fish oil. Aquaculture. 2014;422-423:84–90.Google Scholar

  • 65. Fox ED, Heffernan DS, Cioffi WG, Reichner JS. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity. Crit Care. 2013;17:R226.CrossrefGoogle Scholar

  • 66. Chen Q, Jones D, Stone P, Ching LM, Chamley L. Vitamin C Enhances Phagocytosis of Necrotic Trophoblasts by Endothelial Cells and Protects the Phagocytosing Endothelial Cells from Activation. Placenta. 2009;30:163–8.CrossrefGoogle Scholar

  • 67. Oudemans-van Straaten HM, Man A, de Waard MC. Vitamin C revisited. Crit Care. 2014;18:460.Google Scholar

  • 68. Nathens AB, Neff MJ, Jurkovich GJ, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. 2002;236:814–22.Google Scholar

  • 69. Nagaraja D, Noone ML, Bharatkumar VP, Christopher R. Homocysteine, folate and vitamin B12 in puerperal cerebral venous thrombosis. J Neurol Sci. 2008;272:43–7.Google Scholar

  • 70. Şenol N, NazIroǧlu M, Yürüker V. N-acetylcysteine and selenium modulate oxidative stress, antioxidant vitamin and cytokine values in traumatic brain injury-induced rats. Neurochem Res. 2014;39:685–92.CrossrefGoogle Scholar

  • 71. Navarro-Yepes J, Zavala-Flores L, Anandhan A, et al. Antioxidant gene therapy against neuronal cell death. Pharmacol Ther. 2014;142:206–30.Google Scholar

About the article

Received: 2015-04-08

Accepted: 2015-07-16

Published Online: 2015-08-06

Published in Print: 2015-05-01


Citation Information: The Journal of Critical Care Medicine, ISSN (Online) 2393-1817, DOI: https://doi.org/10.1515/jccm-2015-0014.

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