Skip to main content

Advertisement

Log in

The combination of vitamin D3 and dehydroascorbic acid administration attenuates brain damage in focal ischemia

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

The aim of this study is to determine the protective effects of vitamin D3 and dehydroascorbic acid (DHA), a blood-brain barrier transportable form of vitamin C, against ischemia/reperfusion (I/R) injury on a middle cerebral artery occlusion/reperfusion model of brain since reactive oxygen species play an important role in the pathophysiology of I/R injury in brain. In order to examine antioxidant status and lipid peroxidation, we assayed malondialdehyde (MDA) levels as a marker of lipid peroxidation, and reduced glutathione (GSH) and superoxide dismutase (SOD) enzyme activities as free radical scavenging enzymes in cortex and corpus striatum (CS). Wistar albino rats were divided into five equal groups of each consisting of seven rats: control, I/R, I/R + DHA, I/R + vitamin D3, and I/R + vitamin D3 + dehydroascorbic acid groups. MDA levels were found to be increased in the I/R group, I/R + DHA, and I/R + vitamin D3 groups compared with the control group in both cortex and corpus striatum. However, MDA level were found to be significantly decreased in only I/R + vitamin D3 + DHA group compared with the I/R group in cortex (P < 0.0001). MDA levels were not significantly different in I/R + DHA, and I/R + vitamin D3 groups compared with the I/R group. GSH and SOD enzyme activities were significantly decreased in I/R, I/R + DHA, and I/R + vitamin D3 groups compared with the control group in both cortex and corpus striatum (CS) (P < 0.0001). Whereas, both GSH and SOD activity were increased in I/R + vitamin D3 + DHA group compared with the I/R group in both cortex and CS (P < 0.001 in cortex, P < 0.001 in CS for SOD P < 0.002 in cortex P < 0.03 in CS for GSH). Our results demonstrate that the combination of vitamin D3 and DHA treatment prevent free radical production and dietary supplementation of vitamin D3 and DHA which may be useful in the ischemic cerebral vascular diseases.

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

Similar content being viewed by others

References

  1. Shishido Y, Furushiro M, Hashimoto S, Yokokura T (2001) Effect of nordihydroguaiaretic acid on behavioral impairment and neuronal cell death after forebrain ischemia. Pharmacol Biochem Behav 69(3–4):469–474

    Article  PubMed  CAS  Google Scholar 

  2. Oliver CN, Starke-Reed PE, Stadtman ER, Liu GJ, Carney JM, Floyd RA (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Natl Acad Sci USA 87(13):5144–5147

    Article  PubMed  CAS  Google Scholar 

  3. Ozyurt B, Iraz M, Koca K, Ozyurt H, Sahin S (2006) Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats. Mol Cell Biochem 292(1–2):197–203

    Article  PubMed  CAS  Google Scholar 

  4. Bulkley GB (1987) Free radical-mediated reperfusion injury: a selective review. Br J Cancer Suppl 8:66–73

    PubMed  CAS  Google Scholar 

  5. Scarfiotti C, Fabris F, Cestaro B, Giuliani A (1997) Free radicals, atherosclerosis, ageing, and related dysmetabolic pathologies: pathological and clinical aspects. Eur J Cancer Prev 6(1):31–36

    Article  Google Scholar 

  6. Mahadik SP, Evans D, Lal H (2001) Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 25(3):463–493

    Article  PubMed  CAS  Google Scholar 

  7. Annahazi A, Mracsko E, Sule Z, Karg E, Penke B, Bari F, Farkas E (2007) Pre-treatment and post-treatment with alpha-tocopherol attenuates hippocampal neuronal damage in experimental cerebral hypoperfusion. Eur J Pharmacol 571(2–3):120–128

    Article  PubMed  CAS  Google Scholar 

  8. Bas O, Songur A, Sahin O, Mollaoglu H, Ozen OA, Yaman M, Eser O, Fidan H, Yagmurca M (2007) The protective effect of fish n-3 fatty acids on cerebral ischemia in rat hippocampus. Neurochem Int 50(3):548–554

    Article  PubMed  CAS  Google Scholar 

  9. Altuğ ME, Serarslan Y, Bal R, Kontaş T, Ekici F, Melek IM, Aslan H, Duman T (2008) Caffeic acid phenethyl ester protects rabbit brains against permanent focal ischemia by antioxidant action: a biochemical and planimetric study. Brain Res 1201:135–142

    Article  PubMed  Google Scholar 

  10. Carloni S, Perrone S, Buonocore G, Longini M, Proietti F, Balduini W (2008) Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J Pineal Res 44(2):157–164

    Article  PubMed  CAS  Google Scholar 

  11. Kim EJ, Won R, Sohn JH, Chung MA, Nam TS, Lee HJ, Lee BH (2008) Anti-oxidant effect of ascorbic and dehydroascorbic acids in hippocampal slice culture. Biochem Biophys Res Commun 366(1):8–14

    Article  PubMed  CAS  Google Scholar 

  12. Wilson JX (2002) The physiological role of dehydroascorbic acid. FEBS Lett 527(1–3):5–9

    Article  PubMed  CAS  Google Scholar 

  13. Miura S, Ishida A, Nakajima W, Ohmura A, Kawamura M, Takada G (2006) Intraventricular ascorbic acid administration decreases hypoxic-ischemic brain injury in newborn rats. Brain Res 1095(1):159–166

    Article  PubMed  CAS  Google Scholar 

  14. Santos LF, Freitas RL, Xavier SM, Saldanha GB, Freitas RM (2008) Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures. Pharmacol Biochem Behav 89(1):1–5

    Article  PubMed  CAS  Google Scholar 

  15. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13(3):100–105

    Article  PubMed  CAS  Google Scholar 

  16. Segaert S, Bouillon R (1998) Vitamin D and regulation of gene expression. Curr Opin Clin Nutr Metab Care 1(4):347–354

    Article  PubMed  CAS  Google Scholar 

  17. Prüfer K, Veenstra TD, Jirikowski GF, Kumar R (1999) Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the rat brain and spinal cord. J Chem Neuroanat 16(2):135–145

    Article  PubMed  Google Scholar 

  18. Ibi M, Sawada H, Nakanishi M, Kume T, Katsuki H, Kaneko S, Shimohama S, Akaike A (2001) Protective effects of 1 alpha, 25-(OH)(2)D(3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 40(6):761–771

    Article  PubMed  CAS  Google Scholar 

  19. Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang Y (2001) Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res 904(1):67–75

    Article  PubMed  CAS  Google Scholar 

  20. Wang Y, Chiang YH, Su TP, Hayashi T, Morales M, Hoffer BJ, Lin SZ (2000) Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology 39(5):873–880

    Article  PubMed  CAS  Google Scholar 

  21. Longa EZ, Weinstein S, Carlson S, Cummin R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20(1):84–91

    PubMed  CAS  Google Scholar 

  22. Huang J, Agus DB, Winfree CJ, Kiss S, Mack WJ, McTaggart RA, Choudhri TF, Kim LJ, Mocco J, Pinsky DJ, Fox WD, Israel RJ, Boyd TA, Golde DW, Connolly ES Jr (2001) Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke. Proc Natl Acad Sci USA 98(20):11720–11724

    Article  PubMed  CAS  Google Scholar 

  23. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  PubMed  CAS  Google Scholar 

  24. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70–77

    Article  PubMed  CAS  Google Scholar 

  25. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    PubMed  CAS  Google Scholar 

  26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  27. Stamford JA, Isaac D, Hicks CA, Ward MA, Osborne DJ, O’Neill MJ (1999) Ascorbic acid is neuroprotective against global ischemia in striatum but not hippocampus: histological and voltammetric data. Brain Res 835(2):229–240

    Article  PubMed  CAS  Google Scholar 

  28. Block F, Schmitt W, Schwarz M (1995) The antioxidant LY 231617 ameliorates functional and morphological sequelae induced by global ischemia in rats. Brain Res 694(1–2):308–311

    Article  PubMed  CAS  Google Scholar 

  29. Bemeur C, Ste-Marie L, Desjardins P, Vachon L, Butterworth RF, Hazell AS, Montgomery J (2005) Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat. Neurochem Int 46(5):399–407

    Article  PubMed  CAS  Google Scholar 

  30. Kim EJ, Park YG, Baik EJ, Jung SJ, Won R, Nahm TS, Lee BH (2005) Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes. J Neurosci Res 79(5):670–679

    Article  PubMed  CAS  Google Scholar 

  31. Lin AM, Chen KB, Chao PL (2005) Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS. Ann NY Acad Sci 1053:319–329

    Article  PubMed  CAS  Google Scholar 

  32. Losem-Heinrichs E, Görg B, Redecker C, Schleicher A, Witte OW, Zilles K, Bidmon HJ (2005) 1Alpha, 25-dihydroxy-vitamin D3 in combination with 17 beta-estradiol lowers the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats. Arch Biochem Biophys 439(1):70–79

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fatih Ekici.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ekici, F., Ozyurt, B. & Erdogan, H. The combination of vitamin D3 and dehydroascorbic acid administration attenuates brain damage in focal ischemia. Neurol Sci 30, 207–212 (2009). https://doi.org/10.1007/s10072-009-0038-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-009-0038-6

Keywords

Navigation