Acta Neurochirurgica

, Volume 152, Issue 9, pp 1583–1590 | Cite as

Curcumin improves early functional results after experimental spinal cord injury

  • Berker Cemil
  • Kivanc Topuz
  • Mehmet Nusret Demircan
  • Gokhan Kurt
  • Kagan Tun
  • Murat Kutlay
  • Osman Ipcioglu
  • Zafer Kucukodaci
Experimental research

Abstract

Background

Curcumin is a polyphenol extracted from the rhizome of Curcuma longa and well known as a multifunctional drug with anti-oxidative, anticancerous, and anti-inflammatory activities. The aim of the study was to evaluate and compare the effects of the use of the curcumin and the methylprednisolone sodium succinate (MPSS) functionally, biochemically, and pathologically after experimental spinal cord injury (SCI).

Method

Forty rats were randomly allocated into five groups. Group 1 was performed only laminectomy. Group 2 was introduced 70-g closing force aneurysm clip injury. Group 3 was given 30 mg/kg MPSS intraperitoneally immediately after the trauma. Group 4 was given 200 mg/kg of curcumin immediately after the trauma. Group 5 was the vehicle, and immediately after trauma, 1 mL of rice bran oil was injected. The animals were examined by inclined plane score and Basso–Beattie–Bresnahan scale 24 h after the trauma. At the end of the experiment, spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde (MDA) levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, and catalase (CAT) activity and pathological evaluation.

Findings

Curcumin treatment improved neurologic outcome, which was supported by decreased level of tissue MDA and increased levels of tissue GSH-Px, SOD, and CAT activity. Light microscopy results also showed preservation of tissue structure in the treatment group.

Conclusions

This study showed the neuroprotective effects of curcumin on experimental SCI model. By increasing tissue levels of GSH-Px, SOD, and CAT, curcumin seems to reduce the effects of injury to the spinal cord, which may be beneficial for neuronal survival.

Keywords

Curcumin Methylprednisolone Neuroprotection Oxygen-free radical Spinal cord injury 

Notes

References

  1. 1.
    Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson DK, Demediuk P, Saunders RD, Dugan LL, Means ED, Horrocks LA (1985) Spinal cord injury and protection. Ann Emerg Med 14:816–821PubMedCrossRefGoogle Scholar
  3. 3.
    Balentine JD (1978) Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 39:236–253PubMedGoogle Scholar
  4. 4.
    Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244–256PubMedCrossRefGoogle Scholar
  5. 5.
    Beril Gok H, Solaroglu I, Okutan O, Cimen B, Kaptanoglu E, Palaoglu S (2007) Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats. J Clin Neurosci 14:138–142PubMedCrossRefGoogle Scholar
  6. 6.
    Bhutani MK, Bishnoi M, Kulkarni SK (2009) Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav 92:39–43PubMedCrossRefGoogle Scholar
  7. 7.
    Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322:1405–1411PubMedCrossRefGoogle Scholar
  8. 8.
    Braughler JM, Hall ED (1983) Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester. J Neurosurg 58:538–542PubMedCrossRefGoogle Scholar
  9. 9.
    Cekmen M, Ilbey YO, Ozbek E, Simsek A, Somay A, Ersoz C (2009) Curcumin prevents oxidative renal damage induced by acetaminophen in rats. Food Chem Toxicol 47:1480–1484PubMedCrossRefGoogle Scholar
  10. 10.
    Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900PubMedGoogle Scholar
  11. 11.
    Church DF, Pryor WA (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 64:111–126PubMedCrossRefGoogle Scholar
  12. 12.
    Dickens BF, Mak IT, Weglicki WB (1988) Lysosomal lipolytic enzymes, lipid peroxidation, and injury. Mol Cell Biochem 82:119–123PubMedCrossRefGoogle Scholar
  13. 13.
    Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB, Dumont AS (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24:254–264PubMedCrossRefGoogle Scholar
  14. 14.
    Ferrari R, Ceconi C, Curello S, Cargnoni A, Alfieri O, Pardini A, Marzollo P, Visioli O (1991) Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. Am J Med 91:95–105CrossRefGoogle Scholar
  15. 15.
    Ghoneim AI, Abdel-Naim AB, Khalifa AE, El-Denshary ES (2002) Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacol Res 46:273–279PubMedCrossRefGoogle Scholar
  16. 16.
    Hall ED, Braughler JM (1989) Central nervous system trauma and stroke. II. Physiological and pharmacological evidence for involvement of oxygen radicals and lipid peroxidation. Free Radic Biol Med 6:303–313PubMedCrossRefGoogle Scholar
  17. 17.
    Hall ED (1993) Lipid antioxidants in acute central nervous system injury. Ann Emerg Med 22:1022–1027PubMedCrossRefGoogle Scholar
  18. 18.
    Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623PubMedCrossRefGoogle Scholar
  19. 19.
    Jagetia GC (2007) Radioprotection and radiosensitization by curcumin. Adv Exp Med Biol 595:301–320PubMedCrossRefGoogle Scholar
  20. 20.
    Joe B, Vijaykumar M, Lokesh BR (2004) Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 44:97–111PubMedCrossRefGoogle Scholar
  21. 21.
    Kahraman S, Düz B, Kayali H, Korkmaz A, Oter S, Aydin A, Sayal A (2007) Effects of methylprednisolone and hyperbaric oxygen on oxidative status after experimental spinal cord injury: a comparative study in rats. Neurochem Res 32:1547–1551PubMedCrossRefGoogle Scholar
  22. 22.
    Kalayci M, Coskun O, Cagavi F, Kanter M, Armutcu F, Gul S, Acikgoz B (2005) Neuroprotective effects of ebselen on experimental spinal cord injury in rats. Neurochem Res 30:403–410PubMedCrossRefGoogle Scholar
  23. 23.
    Kaptanoglu E, Caner HH, Sürücü HS, Akbiyik F (1999) Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury. J Neurosurg 91:200–204PubMedGoogle Scholar
  24. 24.
    Kaptanoglu E, Okutan O, Akbiyik F, Solaroglu I, Kilinc A, Beskonakli E (2004) Correlation of injury severity and tissue Evans blue content, lipid peroxidation and clinical evaluation in acute spinal cord injury in rats. J Clin Neurosci 11:879–885PubMedCrossRefGoogle Scholar
  25. 25.
    Kaptanoglu E, Tuncel M, Palaoglu S, Konan A, Demirpençe E, Kilinç K (2000) Comparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury. J Neurosurg 93:77–84PubMedCrossRefGoogle Scholar
  26. 26.
    King VR, Averill SA, Hewazy D, Priestley JV, Torup L, Michael-Titus AT (2007) Erythropoietin and carbamylated erythropoietin are neuroprotective following spinal cord hemisection in the rat. Eur J Neurosci 26:90–100PubMedCrossRefGoogle Scholar
  27. 27.
    Kurt G, Ergün E, Cemil B, Börcek AO, Börcek P, Gülbahar O, Ceviker N (2009) Neuroprotective effects of infliximab in experimental spinal cord injury. Surg Neurol 71:332–336PubMedCrossRefGoogle Scholar
  28. 28.
    Lin MS, Lee YH, Chiu WT, Hung KS (2010) Curcumin Provides Neuroprotection After Spinal Cord Injury. J Surg Res (in press)Google Scholar
  29. 29.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  30. 30.
    Mautes AE, Weinzierl MR, Donovan F, Noble LJ (2000) Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther 80:673–687PubMedGoogle Scholar
  31. 31.
    Motterlini R, Foresti R, Bassi R, Green CJ (2000) Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 28:1303–1312PubMedCrossRefGoogle Scholar
  32. 32.
    Nirmala C, Puvanakrishnan R (1996) Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Mol Cell Biochem 159:85–93PubMedCrossRefGoogle Scholar
  33. 33.
    Okada K, Wangpoengtrakul C, Tanaka T, Toyokuni S, Uchida K, Osawa T (2001) Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice. J Nutr 131:2090–2095PubMedGoogle Scholar
  34. 34.
    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169PubMedGoogle Scholar
  35. 35.
    Priyadarsini KI (1997) Free radical reactions of curcumin in membrane models. Free Radic Biol Med 23:838–843PubMedCrossRefGoogle Scholar
  36. 36.
    Rivlin AS, Tator CH (1978) Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 10:38–43PubMedGoogle Scholar
  37. 37.
    Sahin S, Söğüt S, Özyurt H, Uz E, İlhan A, Akyol Ö (2002) Tissue xanthine oxidase activity and nitric oxide levels after spinal cord ischemia/reperfusion injury in rabbits: comparison of caffeic acid phenethyl ester (CAPE) and methylprednisolone. Neurosci Res Commun 31:111–121CrossRefGoogle Scholar
  38. 38.
    Saunders RD, Dugan LL, Demediuk P, Means ED, Horrocks LA, Anderson DK (1987) Effects of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J Neurochem 49:24–31PubMedCrossRefGoogle Scholar
  39. 39.
    Shen SQ, Zhang Y, Xiang JJ, Xiong CL (2007) Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World J Gastroenterol 13:1953–1961PubMedGoogle Scholar
  40. 40.
    Shoskes D, Lapierre C, Cruz-Correa M, Muruve N, Rosario R, Fromkin B, Braun M, Copley J (2005) Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation: a randomized placebo controlled trial. Transplantation 80:1556–1559PubMedCrossRefGoogle Scholar
  41. 41.
    Shukla PK, Khanna VK, Khan MY, Srimal RC (2003) Protective effect of curcumin against lead neurotoxicity in rat. Hum Exp Toxicol 22:653–658PubMedCrossRefGoogle Scholar
  42. 42.
    Simpson JI, Eide TR, Schiff GA, Clagnaz JF, Hossain I, Tverskoy A, Koski G (1994) Intrathecal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross-clamping. Anesthesiology 81:1493–1499PubMedCrossRefGoogle Scholar
  43. 43.
    Solaroglu I, Kaptanoglu E, Okutan O, Beskonakli E, Attar A, Kilinc K (2005) Magnesium sulfate treatment decreases caspase-3 activity after experimental spinal cord injury in rats. Surg Neurol 64:17–21CrossRefGoogle Scholar
  44. 44.
    Sreejayan RMN (1994) Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 46:1013–1016PubMedCrossRefGoogle Scholar
  45. 45.
    Sun Y (1990) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 8:583–599PubMedCrossRefGoogle Scholar
  46. 46.
    Tator CH (1998) Biology of neurological recovery and functional restoration after spinal cord injury. Neurosurgery 42:696–707PubMedCrossRefGoogle Scholar
  47. 47.
    Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, MacDonald RS, Miller DK, Lubahn DE, Weisman GA, Sun GY (2005) Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 82:138–148PubMedCrossRefGoogle Scholar
  48. 48.
    Yang YB, Piao YJ (2003) Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin 24:703–710PubMedGoogle Scholar
  49. 49.
    Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT (2005) Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's disease. Free Radic Res 39:1119–1125PubMedCrossRefGoogle Scholar
  50. 50.
    Zhao J, Yu S, Zheng W, Feng G, Luo G, Wang L, Zhao Y (2009) Curcumin improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Neurochem Res 35:374–379PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Berker Cemil
    • 1
  • Kivanc Topuz
    • 2
  • Mehmet Nusret Demircan
    • 2
  • Gokhan Kurt
    • 3
  • Kagan Tun
    • 4
  • Murat Kutlay
    • 2
  • Osman Ipcioglu
    • 5
  • Zafer Kucukodaci
    • 6
  1. 1.Department of Neurosurgery, Faculty of MedicineFatih UniversityAnkaraTurkey
  2. 2.Department of Neurosurgery, Haydarpasa Training HospitalGulhane Military Medical AcademyIstanbulTurkey
  3. 3.Department of NeurosurgeryGazi UniversityAnkaraTurkey
  4. 4.Department of NeurosurgeryAnkara Numune Education and Research HospitalAnkaraTurkey
  5. 5.Department of Biochemistry, Haydarpasa Training HospitalGulhane Military Medical AcademyIstanbulTurkey
  6. 6.Department of Pathology, Haydarpasa Training HospitalGulhane Military Medical AcademyIstanbulTurkey

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