J Neurol Surg A Cent Eur Neurosurg 2015; 76(01): 20-24
DOI: 10.1055/s-0034-1371513
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effects of Intrathecal Caffeic Acid Phenethyl Ester and Methylprednisolone on Oxidant/Antioxidant Status in Traumatic Spinal Cord Injuries

Cuneyt Gocmez
1   Department of Neurosurgery, University of Dicle, Diyarbakir, Turkey
Feyzi Celik
2   Department of Anesthesiology, University of Dicle, Diyarbakir, Turkey
Kagan Kamasak
1   Department of Neurosurgery, University of Dicle, Diyarbakir, Turkey
Metin Kaplan
3   Department of Neurosurgery, University of Fırat, Elazığ, Turkey
Ertugrul Uzar
4   Department of Neurology, University of Dicle, Diyarbakir, Turkey
Adalet Arıkanoglu
4   Department of Neurology, University of Dicle, Diyarbakir, Turkey
Osman Evliyaoglu
5   Department of Biochemistry, University of Dicle, Diyarbakir, Turkey
› Author Affiliations
Further Information

Publication History

01 March 2013

13 January 2014

Publication Date:
28 May 2014 (online)


Purpose To examine the effect of intrathecally given caffeic acid phenethyl ester (CAPE) on peroxidation and total oxidant and antioxidant systems, and the effect of intrathecally given methylprednisolone (MP) in spinal cord injury (SCI) models.

Materials and Methods Four groups of 10 rats were formed: (1) Laminectomy, intrathecal saline injection, no SCI (sham: S); (2) Laminectomy, intrathecal saline injection, SCI (control: SCI); (3) Laminectomy, intrathecally given single dose of 3 mg/kg MP, SCISCI (SCI + MP). 4) Laminectomy, intrathecally given single dose of 1 µg/kg CAPE, SCI (SCI + CAPE). Malondialdehyde (MDA), total oxidant activity (TOA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) values in the spinal cord tissue were evaluated.

Results When group S and group SCI were compared, MDA, TOA, and SOD parameters increased post-SCI (p < 0.01). When compared with group SCI, it was observed that CAPE and MP decreased the MDA, TOA, and SOD levels (p < 0.01). This decrease was more pronounced in the SCI + CAPE group. When group S and group SCI were compared, a statistically substantial decrease was observed in the post-SCI TAC levels. When compared with group SCI, it was shown that CAPE and MP treatment substantially increased TAC levels (p < 0.001).

Conclusion Intrathecal injection of both CAPE and MP inhibits lipid peroxidation and increase of oxidants in SCIs.

  • References

  • 1 Jia Z, Zhu H, Li J, Wang X, Misra H, Li Y. Oxidative stress in spinal cord injury and antioxidant-based intervention. Spinal Cord 2012; 50 (4) 264-274
  • 2 Duz B, Kaplan M, Bilgic S, Korkmaz A, Kahraman S. Does hypothermic treatment provide an advantage after spinal cord injury until surgery? An experimental study. Neurochem Res 2009; 34 (3) 407-410
  • 3 Dalgic A, Okay O, Helvacioglu F , et al. Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury. J Neurol Surg A Cent Eur Neurosurg 2013; 74 (3) 136-145
  • 4 Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics 2011; 8 (2) 152-167
  • 5 Aslan A, Cemek M, Eser O , et al. Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study. Eur Spine J 2009; 18 (3) 336-344
  • 6 Topsakal C, Kilic N, Ozveren F , et al. Effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant defense system, paraoxonase (PON1) activities, and homocysteine levels in an animal model of spinal cord injury. Spine 2003; 28 (15) 1643-1652
  • 7 Cayli SR, Kocak A, Yilmaz U , et al. Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury. Eur Spine J 2004; 13 (8) 724-732
  • 8 Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 2012; 1822 (5) 675-684
  • 9 Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 1999; 16 (4) 458-463
  • 10 Hoşnuter M, Gürel A, Babucçu O, Armutcu F, Kargi E, Işikdemir A. The effect of CAPE on lipid peroxidation and nitric oxide levels in the plasma of rats following thermal injury. Burns 2004; 30 (2) 121-125
  • 11 Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett 1993; 329 (1-2) 21-24
  • 12 Kasai M, Fukumitsu H, Soumiya H, Furukawa S. Caffeic acid phenethyl ester reduces spinal cord injury-evoked locomotor dysfunction. Biomed Res 2011; 32 (1) 1-7
  • 13 Uzar E, Sahin O, Koyuncuoglu HR , et al. The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: protective effect of caffeic acid phenethyl ester. Toxicology 2006; 218 (2–3) 125-133
  • 14 Celik F, Gocmez C, Kamasak K , et al. The comparison of neuroprotective effects of intrathecal dexmedetomidine and methylprednisolone in spinal cord injury. Int J Surg 2013; 11 (5) 414-418
  • 15 Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17 (6) 1031-1036
  • 16 Korkmaz HA, Maltepe F, Erbayraktar S , et al. Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat. Anesth Analg 2004; 98 (1) 148-152
  • 17 Senoglu M, Nacitarhan V, Kurutas EB , et al. Intraperitoneal alpha-lipoic acid to prevent neural damage after crush injury to the rat sciatic nerve. J Brachial Plex Peripher Nerve Inj 2009; 4: 22
  • 18 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193 (1) 265-275
  • 19 Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990; 186: 407-421
  • 20 Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37 (4) 277-285
  • 21 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38 (12) 1103-1111
  • 22 Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991; 75 (1) 15-26
  • 23 Collins WF. A review and update of experiment and clinical studies of spinal cord injury. Paraplegia 1983; 21 (4) 204-219
  • 24 Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery 1999; 44 (5) 1027-1039 ; discussion 1039–1040
  • 25 Adibhatla RM, Hatcher JF. Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep 2008; 41 (8) 560-567
  • 26 Muralikrishna Adibhatla R, Hatcher JF. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 2006; 40 (3) 376-387
  • 27 Lin Y, Vreman HJ, Wong RJ, Tjoa T, Yamauchi T, Noble-Haeusslein LJ. Heme oxygenase-1 stabilizes the blood-spinal cord barrier and limits oxidative stress and white matter damage in the acutely injured murine spinal cord. J Cereb Blood Flow Metab 2007; 27 (5) 1010-1021
  • 28 Temiz C, Solmaz I, Tehli O , et al. The effects of splenectomy on lipid peroxidation and neuronal loss in experimental spinal cord ischemia/reperfusion injury. Turk Neurosurg 2013; 23 (1) 67-74
  • 29 Buyukhatipoglu H, Sezen Y, Yildiz A , et al. N-acetylcysteine fails to prevent renal dysfunction and oxidative stress after noniodine contrast media administration during percutaneous coronary interventions. Pol Arch Med Wewn 2010; 120 (10) 383-389
  • 30 Ozgiray E, Serarslan Y, Oztürk OH , et al. Protective effects of edaravone on experimental spinal cord injury in rats. Pediatr Neurosurg 2011; 47 (4) 254-260
  • 31 Pettiford JN, Bikhchandani J, Ostlie DJ, St Peter SD, Sharp RJ, Juang D. A review: the role of high dose methylprednisolone in spinal cord trauma in children. Pediatr Surg Int 2012; 28 (3) 287-294