Skip to main content
Log in

Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Spinal cord injury (SCI) results in rapid and significant oxidative stress. This study was aimed to investigate the possible beneficial effects of Ebselen in comparison with Methylprednisolone in experimental SCI. Thirty six Wistar albino rats (200–250 g) were divided in to six groups; A (control), B (only laminectomy), C (Trauma; laminectomy  + spinal trauma), D (Placebo group; laminectomy  + spinal trauma + serum physiologic), E (Methylprednisolone group; laminectomy  + spinal trauma + Methylprednisolone treated), F (Ebselen group; laminectomy  + spinal trauma + Ebselen treated), containing 6 rats each. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T11–12. After this application, group A, B and C were not treated with any drug. Group D received 1 ml serum physiologic. Group E received 30 mg/kg Methylprednisolone and, Group F received 10 mg/kg Ebselen intraperitoneally (i.p.). Rats were neurologically examined 24 h after trauma and spinal cord tissue samples had been harvested for both biochemical and histopathological evaluation. All rats were paraplegic after SCI except the ones in group A and B. Neurological scores were not different in traumatized rats than that of non-traumatized ones. SCI significantly increased spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to control. Methylprednisolone and Ebselen treatment decreased tissue MDA and PC levels and prevented inhibition of the enzymes SOD, GSH-Px and CAT in the tissues. However, the best results were obtained with Ebselen. In groups C and D, the neurons of the spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in groups E and F were very well protected, but not as good as the control group. The number of neurons in the spinal cord tissues of the groups C and D were significantly less than the groups A, B, E and F. We concluded that the use of Ebselen treatment might have potential benefits in spinal cord tissue damage on clinical grounds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. M. B. Bracken M. J. Shepard W. F. Collins T. R. Holford W. Young D. S. Baskin H. M Eisenberg E. Flamm L. Leo-Summers J. Maroon et al. (1990) ArticleTitleA 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 1405–1411 Occurrence Handle1:STN:280:By%2BB3s7js1A%3D Occurrence Handle2278545

    CAS  PubMed  Google Scholar 

  2. M. B. Bracken M. J. Shepard W. F. Collins T. R Holford D. S. Baskin H. M. Eisenberg E. Flamm L. Leo-Summers J. C. Maroon L. F. Marshall et al. (1992) ArticleTitleMethylprednisolone or naloxone treatment after acute spinal cord injury: one-year follow-up data. Results of the Second National Acute Spinal Cord Injury Study J. Neurosurg. 76 23–31 Occurrence Handle1:STN:280:By2D2sbgtlw%3D Occurrence Handle1727165

    CAS  PubMed  Google Scholar 

  3. D. K. Anderson E. D. Hall (1993) ArticleTitlePathophysiology of spinal cord trauma Ann. Emerg. Med. 22 987–992 Occurrence Handle1:STN:280:ByyB2snpvV0%3D Occurrence Handle8503537

    CAS  PubMed  Google Scholar 

  4. C. H. Tator (1998) ArticleTitleBiology of neurological recovery and functional restoration after spinal cord injury Neurosurgery 42 696–708 Occurrence Handle1:STN:280:DyaK1c3jtlyhsg%3D%3D Occurrence Handle9574633

    CAS  PubMed  Google Scholar 

  5. M. Maiorino A. Roveri M. Coassin F. Ursini (1988) ArticleTitleKinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51) Biochem. Pharmacol. 37 2267–2271 Occurrence Handle1:CAS:528:DyaL1cXksFSku7k%3D Occurrence Handle3377822

    CAS  PubMed  Google Scholar 

  6. A. Muller E. Cadenas P. Graf H. Sies (1984) ArticleTitleA novel biologically active seleno-organic compound I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen) Biochem. Pharmacol. 33 3235–3239 Occurrence Handle1:STN:280:BiqD383nsVw%3D Occurrence Handle6487370

    CAS  PubMed  Google Scholar 

  7. A. Malecki R. Garrido M. P. Mattson B. Henning M. Toborek (2000) ArticleTitle4-hydroxynonenal induces oxidative stress and death of cultured spinal cord neurons J. Neurochem. 74 2278–2287 Occurrence Handle1:CAS:528:DC%2BD3cXjsVKku7s%3D Occurrence Handle10820187

    CAS  PubMed  Google Scholar 

  8. T. Takasago E. E. Peters D. I. Graham H. Masayasu I. M. Macrae (1997) ArticleTitleNeuroprotective efficacy of ebselen an antioxidant with anti-inflammatory actions, in a rodent model of permanent middle cerebral artery occlusion Br. J. Pharmacol. 122 1251–1256 Occurrence Handle1:CAS:528:DyaK2sXnsFWltbk%3D Occurrence Handle9401794

    CAS  PubMed  Google Scholar 

  9. T. Yamaguchi K. Sano K. Takakura I. Saito Y. Shinohara T. Asano H. Yasuhara (1998) ArticleTitleEbselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial Stroke 29 12–17 Occurrence Handle1:CAS:528:DyaK1cXntVKqsg%3D%3D Occurrence Handle9445321

    CAS  PubMed  Google Scholar 

  10. I. Saito T. Asano K. Sano K. Takakura H. Abe T. Yoshimoto H. Kikuchi T. Ohta S. Ishibashi (1998) ArticleTitleNeuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage Neurosurgery 42 269–278 Occurrence Handle1:STN:280:DyaK1c7ktFarsw%3D%3D Occurrence Handle9482177

    CAS  PubMed  Google Scholar 

  11. A. S. Rivlin C. H. Tator (1978) ArticleTitleEffect of duration of acute spinal cord compression in a new acute cord injury model in the rat Surg. Neurol. 10 39–43

    Google Scholar 

  12. A. S. Rivlin C. H. Tator (1977) ArticleTitleObjective clinical assessment of motor function after experimental spinal cord injury in the rat J. Neurosurg. 47 577–581 Occurrence Handle903810

    PubMed  Google Scholar 

  13. O. H. Lowry N. J. Rosebrough R. J. Randall (1951) ArticleTitleProtein measurement with the Folin phenol reagent J. Biol. Chem. 193 265–275 Occurrence Handle1:CAS:528:DyaG38XhsVyrsw%3D%3D Occurrence Handle14907713

    CAS  PubMed  Google Scholar 

  14. H. H. Draper M. Hadley (1990) ArticleTitleMalondialdehyde determination as index of lipid peroxidation Methods Enzymol. 186 421–431 Occurrence Handle2233309

    PubMed  Google Scholar 

  15. R. L. Levine D. Garland C. N. Oliver A. Amici I. Climent A. G. Lenz B. W. Ahn S. Shaltiel E. R. Stadtman (1990) ArticleTitleDetermination of carbonyl content in oxidatively modified proteins Methods Enzymol. 186 464–478 Occurrence Handle1:CAS:528:DyaK3MXksVGhtLY%3D Occurrence Handle1978225

    CAS  PubMed  Google Scholar 

  16. Y. Sun L. W. Oberley Y. Li (1988) ArticleTitleA simple method for clinical assay of superoxide dismutase Clin. Chem. 34 497–500 Occurrence Handle1:CAS:528:DyaL1cXhvVamt7Y%3D Occurrence Handle3349599

    CAS  PubMed  Google Scholar 

  17. H. Aebi (1974) Catalase H. U. Bergmeyer (Eds) Methods of enzymatic analysis Academic Press New York 673–677

    Google Scholar 

  18. D. E. Paglia W. N. Valentine (1967) ArticleTitleStudies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase J. Lab. Clin. Med. 70 158–169 Occurrence Handle1:CAS:528:DyaF2sXks1Wjur8%3D Occurrence Handle6066618

    CAS  PubMed  Google Scholar 

  19. A. I. Faden P. H. Chan S. Longar (1987) ArticleTitleAlterations in lipid metabolism, Na+,K+-ATPase activity, and tissue water content of spinal cord following experimental traumatic injury J. Neurochem. 48 1809–1816 Occurrence Handle1:CAS:528:DyaL2sXksFKrtbg%3D Occurrence Handle3033150

    CAS  PubMed  Google Scholar 

  20. K. Iwasa T. Ikata K. Fukuzawa (1989) ArticleTitleProtective effect of vitamin E on spinal cord injury by compression and concurrent lipid peroxidation Free. Radic. Biol. Med. 6 599–606 Occurrence Handle1:STN:280:BiaA38nitlE%3D Occurrence Handle2753391

    CAS  PubMed  Google Scholar 

  21. D. Liu R. Yang X. Yan D. J. McAdoo (1994) ArticleTitleHydroxyl radicals generated in vivo kill neurons in the rat spinal cord: Electrophysiological, histological, and neurochemical results J. Neurochem. 62 37–44 Occurrence Handle1:CAS:528:DyaK2cXnsVOmtQ%3D%3D Occurrence Handle8263539

    CAS  PubMed  Google Scholar 

  22. S. K. Agrawal M. G. Fehlings (1997) ArticleTitleRole of NMDA and non-NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury J. Neurosci. 17 1055–1063 Occurrence Handle1:CAS:528:DyaK2sXos1yrsA%3D%3D Occurrence Handle8994060

    CAS  PubMed  Google Scholar 

  23. Y. Taoka K. Okajima (1998) ArticleTitleSpinal cord injury in the rat Prog. Neurobiol. 55 1–18 Occurrence Handle9602498

    PubMed  Google Scholar 

  24. E. D. Means D. K. Anderson (1983) ArticleTitleNeuronophagia by leukocytes in experimental spinal cord injury J. Neuropathol. Exp. Neurol. 42 707–719 Occurrence Handle1:STN:280:BiuD3srit1E%3D Occurrence Handle6631457

    CAS  PubMed  Google Scholar 

  25. R. J. Reiter D. X. Tan M. Allegra (2002) ArticleTitleMelatonin: Reducing molecular pathology and dysfunction due to free radicals and associated reactants Neuro. Endocrinol. Lett. Suppl. 1 3–8

    Google Scholar 

  26. G. W. Konat R. C. Wiggins (1985) ArticleTitleEffect of reactive oxygen species on myelin membrane proteins J. Neurochem. 45 1113–1118 Occurrence Handle1:CAS:528:DyaL2MXlsFGntL8%3D Occurrence Handle4031880

    CAS  PubMed  Google Scholar 

  27. E. Kaptanoglu M. Tuncel S. Palaoglu A. Konan E. Demirpence K. Kilinc (2000) ArticleTitleComparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury J. Neurosurg. Spine 93 77–84 Occurrence Handle1:CAS:528:DC%2BD3cXltFShsbc%3D

    CAS  Google Scholar 

  28. E. D. Hall (1993) ArticleTitleLipid antioxidants in acute central nervous system injury Ann. Emerg. Med. 22 1022–1027 Occurrence Handle1:STN:280:ByyB2snpslU%3D Occurrence Handle8503522

    CAS  PubMed  Google Scholar 

  29. R. D. Saunders L. L. Dugan P. Demediuk E. D. Means L. A. Horrocks D. K. Anderson (1987) ArticleTitleEffects 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 24–31 Occurrence Handle1:CAS:528:DyaL2sXktlOntrg%3D Occurrence Handle3108455

    CAS  PubMed  Google Scholar 

  30. H. B. Demopoulos E. S. Flamm D. D. Pietonigro M. L. Seligman (1980) ArticleTitleThe free radical pathology and the microcirculation in the major central nervous system disorders Acta. Physiol. Scand. Suppl. 492 91–119 Occurrence Handle1:CAS:528:DyaL3MXhvV2ltb0%3D Occurrence Handle6939309

    CAS  PubMed  Google Scholar 

  31. E. C. Benzel (1990) ArticleTitleA new rat spinal cord injury model. A ventral compression technique J Spinal Disorders 4 334–338

    Google Scholar 

  32. E. D. Means D. K. Anderson T. R. Waters L. Kalaf (1981) ArticleTitleEffect of methylprednisolone in compression trauma to the feline spinal cord J. Neurosurg. 55 200–208 Occurrence Handle1:CAS:528:DyaL38Xlt1SksLs%3D Occurrence Handle7252543

    CAS  PubMed  Google Scholar 

  33. A. Wendel M. Fausel H. Safayhi G. Tiegs R. Otter (1984) ArticleTitleA novel biologically active seleno-organic compound, II: activity of PZ51 in relation to glutathione peroxidase Biochem. Pharmacol. 33 3241–3245 Occurrence Handle1:CAS:528:DyaL2MXjvFKitw%3D%3D Occurrence Handle6487371

    CAS  PubMed  Google Scholar 

  34. C. W. Nogueira L. N. Rotta G. Zeni D. O. Souza J. B. Rocha (2002) ArticleTitleExposure to ebselen changes glutamate uptake and release by rat brain synaptosomes Neurochem. Res. 27 283–288 Occurrence Handle1:CAS:528:DC%2BD3sXjsFCr Occurrence Handle11958529

    CAS  PubMed  Google Scholar 

  35. A. Muller H. Gabriel H. Sies (1985) ArticleTitleA novel biologically active selenoorganic compound, IV: Protective glutathione-dependent effect of PZ 51 (ebselen) against ADP-Fe induced lipid peroxidation in isoleted hepatocytes Biochem. Pharmacol. 34 1185–1189 Occurrence Handle1:STN:280:BiqC1MbhvFY%3D Occurrence Handle3994741

    CAS  PubMed  Google Scholar 

  36. H. Safayhi G. Tiegs A. Wendel (1985) ArticleTitleA novel biologically active selenoorganic compound, V: inhibition by ebselen (PZ 51) on rat peritoneal neutrophil lipoxygenase Biochem. Pharmacol. 34 2691–2694 Occurrence Handle1:CAS:528:DyaL2MXkvFyntrY%3D Occurrence Handle2990494

    CAS  PubMed  Google Scholar 

  37. V. Ullrich P. Weber F. Meisch F. Appen (1996) ArticleTitleEbselen-binding equilibria between plasma and target proteins Biochem. Pharmacol. 52 15–19 Occurrence Handle1:CAS:528:DyaK28XjvVGntLo%3D Occurrence Handle8678900

    CAS  PubMed  Google Scholar 

  38. S. Ichikawa K. Omura T. Katayama N. Okamura T. Ohtsuka S. Ishibashi H. Masayasu (1987) ArticleTitleInhibition of superoxide anion production in guinea pig polymorphonuclear leukocytes by a seleno-organic compound, ebselen J. Pharmacobio. Dyn. 10 595–597 Occurrence Handle1:CAS:528:DyaL1cXjtFGntQ%3D%3D Occurrence Handle2831335

    CAS  PubMed  Google Scholar 

  39. R. Hattori R. Inoue K. Sase H. Eizawa K. Kosuga T. Aoyama H. Masayasu C. Kawai S. Sasayama Y. Yui (1994) ArticleTitlePreferential inhibition of inducible nitric oxide synthase by ebselen Eur. J. Pharmacol. 267 R1–R2 Occurrence Handle1:CAS:528:DyaK2cXivFSjtL8%3D

    CAS  Google Scholar 

  40. H. Masumoto H. Sies (1996) ArticleTitleThe reaction of ebselen with peroxynitrite Chem. Res. Toxicol. 9 262–267 Occurrence Handle1:CAS:528:DyaK2MXhtVSjs7bP Occurrence Handle8924601

    CAS  PubMed  Google Scholar 

  41. S. Moussaoui M. C. Obinu N. Daniel M. Reibaud V. Blandchard A. Imperato S. Moussaoui M. C. Obinu N. Daniel M. Reibaud V. Blandchard A. Imperato (2000) ArticleTitleThe antioxidant ebselen prevents neurotoxicity and clinical symptoms in a primate model of Parkinson’s disease Exp. Neurol. 166 235–245 Occurrence Handle1:CAS:528:DC%2BD3cXotFCrsLY%3D Occurrence Handle11085889

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Omer Coskun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalayci, M., Coskun, O., Cagavi, F. et al. Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats. Neurochem Res 30, 403–410 (2005). https://doi.org/10.1007/s11064-005-2615-2

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-005-2615-2

Keywords

Navigation