Skip to main content

Oxidative Stress in a Model of Toxic Demyelination in Rat Brain: The Effect of Piracetam and Vinpocetine

Neurochemical Research volume 36, pages 1062–1072 (2011)Cite this article

Abstract

We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). Results: ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. McDonald I (1998) Pathophysiology of multiple sclerosis. In: Compston A, Ebers G, Lassmann H et al (eds) McAlpine’s multiple sclerosis. Churchill Livingstone, London, pp 359–378

    Google Scholar 

  2. Trapp BD, Ransohoff R, Rudick R (1999) Axonal pathology in multiple sclerosis: relationship to neurologic disability. Curr Opin Neurol 12:295–302

    Article  PubMed  CAS  Google Scholar 

  3. Pozzilli C, Romano S, Cannoni S (2002) Epidemiology and current treatment of multiple sclerosis in Europe today. J Rehabil Res Develop 39:175–186

    Google Scholar 

  4. Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150

    Article  PubMed  CAS  Google Scholar 

  5. Beal MF (2002) Oxidatively modified proteins in aging and disease. Free Radic Biol Med 32:797–803

    Article  PubMed  CAS  Google Scholar 

  6. Alimonti A, Ristori G, Giubilei F et al (2007) Serum chemical elements and oxidative status in Alzheimer’s disease, Parkinson disease and multiple sclerosis. NeuroToxicology 28:450–456

    Article  PubMed  CAS  Google Scholar 

  7. Toncev G, Milicic B, Toncev S et al (2002) High-dose methylprednisolone therapy in multiple sclerosis increases serum uric acid levels. Clin Chem Lab Med 40:505–508

    Article  PubMed  CAS  Google Scholar 

  8. Shorvon S (2001) Pyrrolidone derivatives. Lancet 358:1885–1892

    Article  PubMed  CAS  Google Scholar 

  9. Kessler J, Thiel A, Karbe H et al (2000) Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients. Stroke 31:2112–2116

    PubMed  CAS  Google Scholar 

  10. Waegemans T, Wilsher CR, Danniau A et al (2002) Clinical efficacy of piracetam in cognitive impairment: a meta-analysis. Dement Geriatr Cogn Disord 13:217–224

    Article  PubMed  CAS  Google Scholar 

  11. Holinski S, Claus B, Alaaraj N et al (2008) Cerebroprotective effect of piracetam in patients undergoing coronary bypass surgery. Med Sci Monit 14:PI53–PI157

    PubMed  Google Scholar 

  12. Ince Gunal D, Agan K, Afsar N et al (2008) The effect of piracetam on ataxia: clinical observations in a group of autosomal dominant cerebellar ataxia patients. J Clin Pharm Ther 33:175–178

    Article  PubMed  CAS  Google Scholar 

  13. Müller WE, Koch S, Scheuer K et al (1997) Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain. Biochem Pharmacol 53(2):135–140

    Article  PubMed  Google Scholar 

  14. Heiss WD, Ilsen HW, Wagner R et al (1983) Remote functional depression of glucose metabolism in stroke and its alteration by activating drugs. In: Heiss WD, Phelps ME (eds) Positron emission tomography of the brain. Springer, Berlin, pp 162–168

    Google Scholar 

  15. Eckert GP, Cairns NJ, Muller WE (1999) Piracetam reverses hippocampal membrane alterations in Alzheimer’s disease. J Neural Transm 106:757–761

    Article  PubMed  CAS  Google Scholar 

  16. Mingeot-Leclercq MP, Lins L, Bensliman M et al (2003) Piracetam inhibits the lipid-destabilising effect of the amyloid peptide Abeta C-terminal fragment. Biochim Biophys Acta 1609:28–38

    Article  PubMed  CAS  Google Scholar 

  17. DeNoble VJ, Repetti SJ, Gelpke LW et al (1986) Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav 24:1123–1128

    Article  PubMed  CAS  Google Scholar 

  18. Vas A, Gulyas B, Szabo Z et al (2002) Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences. J Neurol Sci 203–204:259–262

    Article  PubMed  Google Scholar 

  19. Van Staveren WCG, Markerink Ittersum M, Steinbusch HW et al (2001) The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat. Brain Res 888:275–286

    Article  PubMed  Google Scholar 

  20. Sitges M, Galvan E, Nekrassov V (2005) Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes. Neurochem Int 46:533–540

    Article  PubMed  CAS  Google Scholar 

  21. Santos MS, Duarte AI, Morbra PI et al (2000) Synaptosomal response to oxidative stress: effect of vinpocetine. Free Radic Res 32:57–66

    Article  PubMed  CAS  Google Scholar 

  22. Horvath BH, Marton Z, Halmosi R et al (2002) In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Clin Neuropharmacol 25:37–42

    Article  PubMed  CAS  Google Scholar 

  23. Giurgea C (1973) The nootropic approach to the pharmacology of the integrative activity of the brain. Cond Reflex 8:108–115

    PubMed  CAS  Google Scholar 

  24. Xerri C, Zennou-Azougui Y, Coq JO (2003) Neuroprotective effects on somatotopic maps resulting from piracetam treatment and environmental enrichment after focal cortical injury. ILAR J 44:110–124

    PubMed  CAS  Google Scholar 

  25. Kalkan E, Keskin F, Kaya B et al (2011) Effects of iloprost and piracetam in spinal cord ischemia–reperfusion injury in the rabbit. Spinal Cord 49:81–86

    Article  PubMed  CAS  Google Scholar 

  26. Pereira C, Agostinho P, Oliveira CR (2000) Vinpocetine attenuates the metabolic dysfunction induced by amyloid β-peptides in PC12 cells. Free Radic Res 33:497–506

    Article  PubMed  CAS  Google Scholar 

  27. Graça DL, Bondan EF, Pereira LA et al. (2001) Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic demyelination of the central nervous system. Arq Neuropsiquiatr 59(2-B):358–361

    Google Scholar 

  28. Mazzanti CM, Spanevello RM, Pereira LB et al (2006) Acetylcholinesterase activity in rats experimentally demyelinated with ethidium bromide and treated with interferon beta. Neurochem Res 31:1027–1034

    Article  PubMed  CAS  Google Scholar 

  29. Ruiz-Larrea MB, Leal AM, Liza M et al (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59:383–388

    Article  PubMed  CAS  Google Scholar 

  30. Koracevic D, Koracevic G, Djordjevic V (2001) Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 54:356–361

    Article  PubMed  CAS  Google Scholar 

  31. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem 82:70–77

    Article  PubMed  CAS  Google Scholar 

  32. Trinder P (1969) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24–25

    CAS  Google Scholar 

  33. Ellman GL, Courtney KD Jr (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharm 7:88–90

    Article  PubMed  CAS  Google Scholar 

  34. Gorum V, Proinov A, Baltescu V et al (1978) Modified Ellman procedure for assay of cholinesterases in crude enzymatic preparation. Anal Biochem 86:324–326

    Article  Google Scholar 

  35. Moshage H, Kok B, Huizenga JR (1995) Nitrite and nitrate determination in plasma: a critical evaluation. Clin Chem 41:892–896

    PubMed  CAS  Google Scholar 

  36. Liu R, Lui IY, Bi X et al (2003) Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc Natl Acad Sci USA 100:8526–8531

    Article  PubMed  CAS  Google Scholar 

  37. Besler HT, Comoğlu S (2006) Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci 6:189–196

    Article  Google Scholar 

  38. Cnubben NHP, Rietjens IMCM, Wortelboer H et al (2001) The interplay of glutathione related processes in antioxidant defense. Environ Toxicol Pharmacol 10:141–152

    Article  CAS  Google Scholar 

  39. Ng F, Berk M, Dean O et al (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11:851–876

    Article  PubMed  CAS  Google Scholar 

  40. Schulz JB, Lindenau J, Seyfried J (2000) Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 267:4904–4911

    Article  PubMed  CAS  Google Scholar 

  41. Brown GC (2010) Nitric oxide and neuronal death. Nitric Oxide 23:153–165

    Article  PubMed  CAS  Google Scholar 

  42. Liñares D, Taconis M, Maña P et al (2006) Neuronal nitric oxide synthase plays a key role in CNS demyelination. J Neurosci 26:12672–12681

    Article  PubMed  Google Scholar 

  43. Speciale L, Sarasella M, Ruzzante S et al (2000) Endothelin and nitric oxide levels in cerebrospinal fluid of patients with multiple sclerosis. J Neuro Virol 6(Suppl 20):S62–S66

    CAS  Google Scholar 

  44. Ramsaransing GS, Teelken A, Arutjunyan AV et al (2004) Peripheral blood leukocyte NO production in MS patients with a benign vs progressive course. Neurology 62(2):239–242

    PubMed  CAS  Google Scholar 

  45. Moncada S, Bolaños JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97:1676–1689

    Article  PubMed  CAS  Google Scholar 

  46. Ozkan S, Ikizceli I, Sözüer EM et al (2008) The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock. Ulus Travma Acil Cerrahi Derg 14:277–283

    PubMed  Google Scholar 

  47. Ghiselli A, Serafini M, Natella F et al (2000) Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med 29:1106–1114

    Article  PubMed  CAS  Google Scholar 

  48. Young IS (2001) Measurement of total antioxidant capacity. J Clin Pathol 54:339

    Google Scholar 

  49. Costantini D, Verhulst S (2009) Does high antioxidant capacity indicate low oxidative stress? Funct Ecol 23:506–509

    Article  Google Scholar 

  50. Gouliaev AH, Senning A (1994) Piracetam and other structurally related nootropics. Brain Res Rev 19:180–222

    Article  PubMed  CAS  Google Scholar 

  51. Müller WE, Eckert GP, Eckert A (1999) Piracetam: novelty in a unique mode of action. Pharmacopsychiatry 32(Suppl 1):2–9

    Article  PubMed  Google Scholar 

  52. Keil U, Scherping I, Hauptmann S et al (2006) Piracetam improves mitochondrial dysfunction following oxidative stress. Br J Pharmacol 147:199–208

    Article  PubMed  CAS  Google Scholar 

  53. Kurz C, Ungerer I, Lipka U et al (2010) The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide. Br J Pharmacol 160:246–257

    Article  PubMed  CAS  Google Scholar 

  54. Gabryel B, Adamek M, Pudełko A et al (2002) Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. Neurotoxicology 23:19–31

    Article  PubMed  CAS  Google Scholar 

  55. Trejo F, Nekrassov V, Sitges M (2001) Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings. Brain Res 909:59–67

    Article  PubMed  CAS  Google Scholar 

  56. Wustmann C, Blaschke M, Rudolph E et al (1990) Influence of nootropic drugs on the age-dependent potassium-coupling of transmitter release. Biomed Biochim Acta 49:619–624

    PubMed  CAS  Google Scholar 

  57. Stancheva SL, Alova LG (1994) Biogenic monoamine uptake by rat brain synaptosomes during aging. Effects of nootropic drugs. Gen Pharmacol 25:981–987

    PubMed  CAS  Google Scholar 

  58. Budygin EA, Gaĭnetdinov RR, Titov DA et al (1996) The effect of a low dose of piracetam on the activity of the dopaminergic system in the rat striatum. Eksp Klin Farmakol 59:6–8

    PubMed  CAS  Google Scholar 

  59. Barzilai A, Melamed E, Shirvan A (2001) Is there a rationale for neuroprotection against dopamine toxicity in Parkinson’s disease? Cell Mol Neurobiol 21:215–235

    Article  PubMed  CAS  Google Scholar 

  60. Gulyás B, Halldin C, Sandell J et al (2002) PET studies on the brain uptake and regional distribution of [11C]vinpocetine in human subjects. Acta Neurol Scand 106:325–332

    Article  PubMed  Google Scholar 

  61. Grau M, Montero JL, Balasch J (1987) Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat. Gen Pharmacol 18:205–211

    PubMed  CAS  Google Scholar 

  62. Piercey MF, Vogelsang GD, Franklin SR et al (1987) Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces. Brain Res 424:1–9

    Article  PubMed  CAS  Google Scholar 

  63. Heiss WD, Hebold I, Klinkhammer P et al (1988) Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by positron emission tomography. J Cereb Blood Flow Metab 8:613–617

    Article  PubMed  CAS  Google Scholar 

  64. Kaufer D, Friedman A, Seidman S et al (1998) Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 393:373–377

    Article  PubMed  CAS  Google Scholar 

  65. Tagliari B, Tagliari AP, Schmitz F et al (2011) Chronic variable stress alters inflammatory and cholinergic parameters in hippocampus of Rats. Neurochem Res 36:487–493

    Article  PubMed  CAS  Google Scholar 

  66. Bond CE, Greenfield SA (2007) Multiple cascade effects of oxidative stress on astroglia. Glia 55:1348–1361

    Article  PubMed  Google Scholar 

  67. Tarsy D (2006) Initial treatment of Parkinson’s disease. Curr Treat Options Neurol 8:224–235

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Toxicology and Narcotics, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Omar M. E. Abdel-Salam & Neveen A. Salem

  2. Department of Pharmacology, National Research Centre, Cairo, Egypt

    Omar M. E. Abdel-Salam & Amany A. Sleem

  3. Department of Physiology, National Research Centre, Cairo, Egypt

    Yasser A. Khadrawy

Authors
  1. Omar M. E. Abdel-Salam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasser A. Khadrawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neveen A. Salem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amany A. Sleem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Omar M. E. Abdel-Salam.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Abdel-Salam, O.M.E., Khadrawy, Y.A., Salem, N.A. et al. Oxidative Stress in a Model of Toxic Demyelination in Rat Brain: The Effect of Piracetam and Vinpocetine. Neurochem Res 36, 1062–1072 (2011). https://doi.org/10.1007/s11064-011-0450-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0450-1

Keywords

  • Toxic demyelination
  • Ethidium bromide
  • Vinpocetine
  • Piracetam
  • Rat brain