Skip to main content
Log in

Efficacy of N-acetylcysteine on neuroclinical, biochemical, and histopathological parameters in experimental spinal cord trauma: comparison with methylprednisolone

  • Original Article
  • Published:
European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

An Erratum to this article was published on 29 January 2014

Abstract

Background

N-acetylcysteine (NAC) is an antioxidant agent that has been shown to have beneficial effects when treating various diseases. The aim of this study was to investigate the effects of NAC on spinal cord injury in an experimental rat model.

Methods

A total of 48 adult male wistar albino rats were divided into six groups. Group C included the control rats, group L included the rats that underwent laminectomy, and group T included the rats in which spinal cord trauma was induced by the weight-drop method after laminectomy. Groups M (the methylprednisolone group), N (the NAC group), and MN (the methylprednisolone + NAC group) were the treatment groups. In the fourth group (group M), 30 mg/kg methylprednisolone (MP) was administered as a bolus intraperitoneally (IP), and a standard MP treatmentat a dose of 5.4 mg/kg was applied for 24 h. In the fifth group (group N), only 300 mg/kg NAC was administered as a bolus IP. In the sixth group (group MN), the standard MP treatment and a single 300 mg/kg dose of NAC were administered as a bolus IP. The motor functions of the rats were evaluated on the 1st, 7th, and 14th days using the inclined plane test defined by Rivlin and Tator and the motor scale defined by Gale et al. Spinal cord samples were obtained on the 14th day. The samples were evaluated using pathological and biochemical analysis.

Results

In the neuroclinical assessment, no differences were observed between groups T and M in terms of motor improvement. However, statistically significant differences were observed between group T and groups N and MN (p < 0.001, p = 0.01, respectively). Statistically significant differences were also seen between group M and groups N and MN on the 1st and 7th days (p < 0.017, p < 0.01, respectively). Additionally, when groups N and MN were compared with groups T and M,the pathological and biochemical analyses were found to be statistically different (p < 0.05, p < 0.001, respectively).

Conclusion

It was concluded that NAC treatment and the combined NAC + MP treatment may be more useful for healing in rats with experimental spinal cord injury in terms of neuroclinical, pathological, and biochemical results than MP-only therapy.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

NAC:

N-acetylcysteine

IP:

Intraperitoneally

MP:

Methylprednisolone

SCI:

Spinal cord injury

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

GPX:

Glutathione peroxidase

PC:

Protein carbonyl

TBA:

Thiobarbituric acid

PMNL:

Polymorphonuclear leukocytes

References

  1. Harkey HL III, White EA, Tibbs RE Jr, et al. A clinician’s view of spinal cord injury. Anat Rec B New Anat. 2003;271:41–8.

    Article  PubMed  Google Scholar 

  2. National Spinal Cord Injury Statistical Center. J Spinal Cord Med. 2012;36(1):1–2. doi:10.1179/1079026813Z.000000000136.

    Google Scholar 

  3. Kwon BK, Oxland TR, Tetzlaf W. Animal models used in spinal cord regeneration research. Spine. 2002;27:1504–10.

    Article  PubMed  Google Scholar 

  4. Ates O, Cayli S, Altinoz E, et al. Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury. Acta Pharmacol Sin. 2006;27:1317–25.

    Article  CAS  PubMed  Google Scholar 

  5. Hanci V, Kerimoğlu A, Koca K, et al. The biochemical effectiveness of N-acetylcysteine in experimental spinal cord injury in rats. TJTES. 2010;16:15–21.

    PubMed  Google Scholar 

  6. Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev. 2012;18(1):CD001046. doi:10.1002/14651858.CD001046.pub2.

    Google Scholar 

  7. Walters BC, Hadley MN, Hurlbert RJ, et al. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery. 2013;60:82–91. doi:10.1227/01.neu.0000430319.32247.7f.

    Article  PubMed  Google Scholar 

  8. Qian T, Guo X, Levi AD, et al. Highdose methylprednisolone may cause myopathy in acute spinal cord injury patients. Spinal Cord. 2005;43:199–203.

    Article  CAS  PubMed  Google Scholar 

  9. Onifer SM, Rabchevsky AG, Scheff SW. Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J. 2007;48:385–95.

    Article  CAS  PubMed  Google Scholar 

  10. Panjabi MM. Experimental spinal cord trauma. A biomechanical viewpoint. Paraplegia. 1987;25:217–20.

    Article  CAS  PubMed  Google Scholar 

  11. Tator CH. Review of experimental spinal cord injury with emphasis on the local and systemic circulatory effects. Neurochirurgie. 1991;37:291–302.

    CAS  PubMed  Google Scholar 

  12. Gale K, Kerasidis H, Wrathall JR. Spinal cord contusions in the rat: behavioral analysis of functional neurologic impairment. Exp Neurol. 1985;88:123–34.

    Article  CAS  PubMed  Google Scholar 

  13. Ha KY, Kim YH, Rhyu KW, et al. Pregabalin as a neuroprotector after spinal cord injury in rats. Eur Spine J. 2008;17:864–72.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Irmak MK, Koltuksuz U, Kutlu NO, et al. The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with alpha-tocopherol in rat kidneys. Urol Res. 2001;29:190–3.

    Article  CAS  PubMed  Google Scholar 

  15. Lowry OH, Rosebrough NJ, Farr AL, et al. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75.

    CAS  PubMed  Google Scholar 

  16. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407–21.

    Article  CAS  PubMed  Google Scholar 

  17. Altunoluk B, Soylemez H, Bakan V, Ciralik H, Tolun FI. Protective effects of zofenopril on testicular torsion and detorsion ınjury in rats. Urol J. 2011;8:313–9.

    Google Scholar 

  18. Stein DM, Roddy V, Marx J, et al. Emergency neurological life support: traumatic spine injury. Neurocrit Care. 2012;17:102–11.

    Google Scholar 

  19. Bracken MB, Shepard MJ, Collins WF, et al. 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. 1990;322:1405–11.

    Google Scholar 

  20. Dumont RJ, Verma S, Okonkwo DO, et al. Acute spinal cord injury. Part II: contemporary pharmacotherapy. Clin Neuropharmocol. 2001;24:265–79.

    Google Scholar 

  21. Sinha K, Deogonakar M, Jagannathan NR, et al. Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats. Eur J Pharmacol. 2001;428:185–92.

    Google Scholar 

  22. Hicdonmez T, Kanter M, Tiryaki M, et al. Neuroprotective effects of N-acetylcysteine on experimental closed head trauma in rats. Neurochem Res. 2006;31:473–81.

    Google Scholar 

  23. Kaynar MY, Erdinçler P, Tadayyon E, et al. Effect of nimodipine and N-acetylcysteine on lipid peroxidation after experimental spinal cord injury. Neurosurg Rev. 1998;21:260–4.

    Google Scholar 

  24. Dringen R, Hamprecht B. N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain. Neurosci Lett. 1999;259:79–82.

    Google Scholar 

  25. Arakawa M, Ito Y. N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. Cerebellum. 2007;6:308–14.

    Google Scholar 

  26. Rabchevsky AG, Patel SP, Springer JE. Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward? Pharmacol Ther. 2011;132:15–29.

    Google Scholar 

  27. Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics. 2011;8:152–67.

    Google Scholar 

  28. Khan M, Sekhon B, Jatana M, et al. Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res. 2004;76:519–27.

    Google Scholar 

  29. Prescott L. Oral or intravenous N-acetylcysteine for acetaminophen poisoning? Ann Emerg Med. 2005;45:409–13.

    Google Scholar 

  30. Thomale UW, Griebenow M, Kroppenstedt SN, et al. The effect of N-acetylcysteine on posttraumatic changes after controlled cortical impact in rats. Intensive Care Med. 2006;32:149–55.

    Google Scholar 

  31. Boga M, Discigil B, Ozkisacik EA, et al. The combined effect of iloprost and N-acetylcysteine in preventing spinal cord ischemia in rabbits. Eur J Vasc Endovasc Surg. 2006;31:366–72.

    Google Scholar 

  32. Rahman A, Ustundag B, Burma O, et al. Neuroprotective effect of regional carnitine on spinal cord ischemia-reperfusion injury. Eur J Cardiothorac Surg. 2001;20:65–70.

    Google Scholar 

  33. Cakir O, Erdem K, Oruc A, et al. Neuroprotective effect of N-acetylcysteine and hypothermia on the spinal cord ischemia-reperfusion injury. Cardiovasc Surg. 2003;11:375–9.

    Google Scholar 

  34. Yi JH, Hazell AS. N-acetylcysteine attenuates early induction of heme oxygenase-1 following traumatic brain injury. Brain Res. 2005;1033:13–9.

    Google Scholar 

  35. Scafidi S, Racz J, Hazelton J, et al. Neuroprotection by acetyl-l-carnitine after traumatic injury to the immature rat brain. Dev Neurosci. 2010;32:480–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Thanks to Bushra Rashid, Ph.D., ELS, and “Scribendi” for language polishing, and to Salih Ergocen for revising the content statistically.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to U. Y. Çavuş.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Çavuş, U.Y., Yılmaz, A., Aytekin, M.N. et al. Efficacy of N-acetylcysteine on neuroclinical, biochemical, and histopathological parameters in experimental spinal cord trauma: comparison with methylprednisolone. Eur J Trauma Emerg Surg 40, 363–371 (2014). https://doi.org/10.1007/s00068-013-0349-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00068-013-0349-4

Keywords

Navigation