Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury

  • Kalemci, Orhan (Department of Neurosurgery, School of Medicine and Hospital, Dokuz Eylul University) ;
  • Aydin, Hasan Emre (Department of Pharmacology, Eskisehir Osmangazi University) ;
  • Kizmazoglu, Ceren (Department of Neurosurgery, School of Medicine and Hospital, Dokuz Eylul University) ;
  • Kaya, Ismail (Department of Neurosurgery, Kilis State Hospital) ;
  • Yilmaz, Hulya (Department of Biostatistics and Medical Informatics, Eskisehir Osmangazi University) ;
  • Arda, Nuri M (Department of Neurosurgery, School of Medicine and Hospital, Dokuz Eylul University)
  • Received : 2016.05.31
  • Accepted : 2016.11.29
  • Published : 2017.05.01
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Abstract

Objective : The aim of this study to investigate the normal values of erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO and hematocrit levels after acute severe traumatic brain injury (TBI) in rat model. Methods : A weight-drop impact acceleration model of TBI was used on 40 male Wistar rats. The animals were divided into sham (group I), TBI (group II), TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase, catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two-way repeated measures analysis of variance and Tukey's test were used for statistical analysis. Results : The malondialdehyde levels decreased significantly after administration of quercetin and mannitol compared with those in group II. Catalase and glutathione peroxidase levels increased significantly in groups III and IV. Serum EPO levels decreased significantly after mannitol but not after quercetin administration. Serum hematocrit levels did not change significantly after quercetin and mannitol administration 1 hour after trauma. However, mannitol administration decreased serum hematocrit levels significantly after 4 hour. Conclusion : This study suggests that quercetin may be a good alternative treatment for TBI, as it did not decrease the EPO levels.

Keywords

References

  1. Akdemir Ozisik P, Oruckaptan H, Ozdemir Geyik P, Misirlioglu M, Sargon MF, Kilinc K, et al. : Effect of erythropoietin on brain tissue after experimental head trauma in rats. Surg Neurol 68 : 547-555; discussion 555, 2007 https://doi.org/10.1016/j.surneu.2007.01.030
  2. Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA : Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer's disease. J Nutr Biochem 20 : 269-275, 2009 https://doi.org/10.1016/j.jnutbio.2008.03.002
  3. Balak N, Isiksacan N, Turkoglu R : Does serum osmolarity change as a result of the reflex neuroprotective mechanism of cerebral osmo-regulation after minor head trauma? J Korean Neurosurg Soc 45 : 151-156, 2009 https://doi.org/10.3340/jkns.2009.45.3.151
  4. Basarslan SK, Gocmez C, Kamasak K, Ekici MA, Ulutabanca H, Dogu Y, et al. : The effects of erythropoietin, dextran and saline on brain edema and lipid peroxidation in experimental head trauma. Ulus Travma Acil Cerrahi Derg 21 : 235-240, 2015
  5. Bischoff SC : Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 11 : 733-740, 2008 https://doi.org/10.1097/MCO.0b013e32831394b8
  6. Blaha M, Schwab J, Vajnerova O, Bednar M, Vajner L, Michal T : Intracranial pressure and experimental model of diffuse brain injury in rats. J Korean Neurosurg Soc 47 : 7-10, 2010 https://doi.org/10.3340/jkns.2010.47.1.7
  7. Bleilevens C, Roehl AB, Goetzenich A, Zoremba N, Kipp M, Dang J, et al. : Effect of anesthesia and cerebral blood flow on neuronal injury in a rat middle cerebral artery occlusion (MCAO) model. Exp Brain Res 224 : 155-164, 2013 https://doi.org/10.1007/s00221-012-3296-0
  8. Bouzat P, Millet A, Boue Y, Pernet-Gallay K, Trouve-Buisson T, Gaide-Chevronnay L, et al. : Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin. Crit Care Med 41 : 1316-1324, 2013 https://doi.org/10.1097/CCM.0b013e31827ca64e
  9. Cole TB : Global road safety crisis remedy sought: 1.2 million killed, 50 million injured annually. JAMA 291 : 2531-2532, 2004 https://doi.org/10.1001/jama.291.21.2531
  10. Davis AE : Mechanisms of traumatic brain injury: biomechanical, structural and cellular considerations. Crit Care Nurs Q 23 : 1-13, 2000
  11. DeWitt DS, Jenkins LW, Prough DS : Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury. New Horiz 3 : 376-383, 1995
  12. Dong YS, Wang JL, Feng DY, Qin HZ, Wen H, Yin ZM, et al. : Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int J Med Sci 11 : 282-290, 2014 https://doi.org/10.7150/ijms.7634
  13. Dugas AJ Jr, Castaneda-Acosta J, Bonin GC, Price KL, Fischer NH, Winston GW : Evaluation of the total peroxyl radical-scavenging capacity of flavonoids: structure-activity relationships. J Nat Prod 63 : 327-331, 2000 https://doi.org/10.1021/np990352n
  14. Faria A, Pestana D, Teixeira D, Azevedo J, De Freitas V, Mateus N, et al. : Flavonoid transport across RBE4 cells: a blood-brain barrier model. Cell Mol Biol Lett 15 : 234-241, 2010
  15. Fernandez SP, Wasowski C, Loscalzo LM, Granger RE, Johnston GA, Paladini AC, et al. : Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol 539 : 168-176, 2006 https://doi.org/10.1016/j.ejphar.2006.04.004
  16. Ferrali M, Signorini C, Ciccoli L, Bambagioni S, Rossi V, Pompella A, et al. : Protection of erythrocytes against oxidative damage and autologous immunoglobulin G (IgG) binding by iron chelator fluor-benzoil-pyridoxal hydrazone. Biochem Pharmacol 59 : 1365-1373, 2000 https://doi.org/10.1016/S0006-2952(00)00273-2
  17. Fisher JW : Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood) 228 : 1-14, 2003 https://doi.org/10.1177/153537020322800101
  18. Ghajar J : Traumatic brain injury. Lancet 356 : 923-929, 2000 https://doi.org/10.1016/S0140-6736(00)02689-1
  19. Grasso G, Alafaci C, Buemi M. Erythropoietin in traumatic brain injury: an answer will come soon. World Neurosurg 84 : 1491-1492, 2015 https://doi.org/10.1016/j.wneu.2015.05.056
  20. Grasso G, Sfacteria A, Meli F, Fodale V, Buemi M, Iacopino DG : Neuroprotection by erythropoietin administration after experimental traumatic brain injury. Brain Res 1182 : 99-105, 2007 https://doi.org/10.1016/j.brainres.2007.08.078
  21. Haleagrahara N, Radhakrishnan A, Lee N, Kumar P : Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rats. Eur J Pharmacol 621 : 46-52, 2009 https://doi.org/10.1016/j.ejphar.2009.08.030
  22. Harnly JM, Doherty RF, Beecher GR, Holden JM, Haytowitz DB, Bhagwat S, et al. : Flavonoid content of U.S. fruits, vegetables, and nuts. J Agric Food Chem 54 : 9966-9977, 2006 https://doi.org/10.1021/jf061478a
  23. Hartley CE, Varma M, Fischer JP, Riccardi R, Strauss JA, Shah S, et al. : Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma. J Neurosurg 109 : 708-714, 2008 https://doi.org/10.3171/JNS/2008/109/10/0708
  24. Havsteen BH : The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96 : 67-202, 2002 https://doi.org/10.1016/S0163-7258(02)00298-X
  25. Hellewell SC, Yan EB, Alwis DS, Bye N, Morganti-Kossmann MC : Erythropoietin improves motor and cognitive deficit, axonal pathology, and neuroinflammation in a combined model of diffuse traumatic brain injury and hypoxia, in association with upregulation of the erythropoietin receptor. J Neuroinflammation 10 : 156, 2013
  26. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D : Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342 : 1007-1011, 1993 https://doi.org/10.1016/0140-6736(93)92876-U
  27. Jager AK, Saaby L : Flavonoids and the CNS. Molecules 16 : 1471-1485, 2011 https://doi.org/10.3390/molecules16021471
  28. Juul SE, Beyer RP, Bammler TK, McPherson RJ, Wilkerson J, Farin FM : Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatr Res 65 : 485-492, 2009 https://doi.org/10.1203/PDR.0b013e31819d90c8
  29. Kaufmann AM, Cardoso ER : Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 77 : 584-589, 1992 https://doi.org/10.3171/jns.1992.77.4.0584
  30. Kook D, Wolf AH, Yu AL, Neubauer AS, Priglinger SG, Kampik A, et al. : The protective effect of quercetin against oxidative stress in the human RPE in vitro. Invest Ophthalmol Vis Sci 49 : 1712-1720, 2008 https://doi.org/10.1167/iovs.07-0477
  31. Lee JY, Lee CY, Kim HR, Lee CH, Kim HW, Kim JH : A role of serumbased neuronal and glial markers as potential predictors for distinguishing severity and related outcomes in traumatic brain injury. J Korean Neurosurg Soc 58 : 93-100, 2015 https://doi.org/10.3340/jkns.2015.58.2.93
  32. Maas AI, Stocchetti N, Bullock R : Moderate and severe traumatic brain injury in adults. Lancet Neurol 7 : 728-741, 2008 https://doi.org/10.1016/S1474-4422(08)70164-9
  33. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K : A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80 : 291-300, 1994 https://doi.org/10.3171/jns.1994.80.2.0291
  34. Middleton E Jr, Kandaswami C, Theoharides TC : The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52 : 673-751, 2000
  35. Myhrstad MC, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JO : Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med 32 : 386-393, 2002 https://doi.org/10.1016/S0891-5849(01)00812-7
  36. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al. : Clinical trials in head injury. J Neurotrauma 19 : 503-557, 2002 https://doi.org/10.1089/089771502753754037
  37. Ossola B, Kaariainen TM, Mannisto PT : The multiple faces of quercetin in neuroprotection. Expert Opin Drug Saf 8 : 397-409, 2009 https://doi.org/10.1517/14740330903026944
  38. Park JE, Kim SH, Yoon SH, Cho KG, Kim SH : Risk factors predicting unfavorable neurological outcome during the early period after traumatic brain injury. J Korean Neurosurg Soc 45 : 90-95, 2009 https://doi.org/10.3340/jkns.2009.45.2.90
  39. Peng W, Xing Z, Yang J, Wang Y, Wang W, Huang W : The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models. J Neurosurg 121 : 653-664, 2014 https://doi.org/10.3171/2014.6.JNS132577
  40. Rangel-Ordonez L, Noldner M, Schubert-Zsilavecz M, Wurglics M : Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb $761^{(R)}$ Planta Med 76 : 1683-1690, 2010 https://doi.org/10.1055/s-0030-1249962
  41. Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC, et al. : Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA 312 : 36-47, 2014 https://doi.org/10.1001/jama.2014.6490
  42. Rossi R, Dalle-Donne I, Milzani A, Giustarini D : Oxidized forms of glutathione in peripheral blood as biomarkers of oxidative stress. Clin Chem 52 : 1406-1414, 2006 https://doi.org/10.1373/clinchem.2006.067793
  43. Schober ME, Requena DF, Block B, Davis LJ, Rodesch C, Casper TC, et al. : Erythropoietin improved cognitive function and decreased hippocampal caspase activity in rat pups after traumatic brain injury. J Neurotrauma 31 : 358-369, 2014 https://doi.org/10.1089/neu.2013.2922
  44. Schultke E, Kamencic H, Zhao M, Tian GF, Baker AJ, Griebel RW, et al. : Neuroprotection following fluid percussion brain trauma: a pilot study using quercetin. J Neurotrauma 22 : 1475-1484, 2005 https://doi.org/10.1089/neu.2005.22.1475
  45. Tango HK, Schmidt AP, Mizumoto N, Lacava M, Cruz RJ Jr, Auler JO Jr : Low hematocrit levels increase intracranial pressure in an animal model of cryogenic brain injury. J Trauma 66 : 720-726, 2009 https://doi.org/10.1097/TA.0b013e3181719b35
  46. Thurman D, Guerrero J : Trends in hospitalization associated with traumatic brain injury. JAMA 282 : 954-957, 1999 https://doi.org/10.1001/jama.282.10.954
  47. Velly L, Pellegrini L, Guillet B, Bruder N, Pisano P : Erythropoietin 2nd cerebral protection after acute injuries: a double-edged sword? Pharmacol Ther 128 : 445-459, 2010 https://doi.org/10.1016/j.pharmthera.2010.08.002
  48. Yang T, Kong B, Gu JW, Kuang YQ, Cheng L, Yang WT, et al. : Antiapoptotic and anti-oxidative roles of quercetin after traumatic brain injury. Cell Mol Neurobiol 34 : 797-804, 2014 https://doi.org/10.1007/s10571-014-0070-9
  49. Yilmaz N, Dulger H, Kiymaz N, Yilmaz C, Gudu BO, Demir I : Activity of mannitol and hypertonic saline therapy on the oxidant and antioxidant system during the acute term after traumatic brain injury in the rats. Brain Res 1164 : 132-135, 2007 https://doi.org/10.1016/j.brainres.2007.06.017
  50. Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C : Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 85 : 180-192, 2003 https://doi.org/10.1046/j.1471-4159.2003.01652.x
  51. Zhang Y, Xiong Y, Mahmood A, Meng Y, Qu C, Schallert T, et al. : Therapeutic effects of erythropoietin on histological and functional outcomes following traumatic brain injury in rats are independent of hematocrit. Brain Res 1294 : 153-64, 2009 https://doi.org/10.1016/j.brainres.2009.07.077

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