Advertisement

Journal of Membrane Biology

, Volume 233, Issue 1–3, pp 135–142 | Cite as

Melatonin Modulates Hippocampus NMDA Receptors, Blood and Brain Oxidative Stress Levels in Ovariectomized Rats

  • Müfide Dilek
  • Mustafa Nazıroğlu
  • H. Baha Oral
  • İ. Suat Övey
  • Mustafa Küçükayaz
  • M. Tamer Mungan
  • H. Yusuf Kara
  • Recep Sütçü
Article

Abstract

We investigated the effects of melatonin administration on ovariectomy-induced oxidative toxicity and N-methyl-d-aspartate receptor (NMDAR) subunits in the blood of rats. Thirty-two rats were studied in three groups. The first and second groups were control and ovariectomized rats. Melatonin was daily administrated to the ovariectomized rats in the third group for 30 days. Blood, brain cortical and hippocampal samples were taken from the three groups after 30 days. Brain cortical, erythrocyte and plasma lipid peroxidation (LP) levels were higher in the ovariectomized group than in controls, although the LP level was decreased in the ovariectomized group with melatonin treatment. Brain cortical and plasma concentrations of vitamins A, C and E as well as the NMDAR 2B subunit were lower in the ovariectomized group than in controls, although, except for plasma vitamin C, they were increased by the treatment. Brain cortical and erythrocyte reduced glutathione (GSH) levels were lower in the ovariectomized group than in controls, although erythrocyte GSH levels were higher in the melatonin group than in the ovariectomized group. Brain cortical and erythrocyte glutathione peroxidase activity and NMDAR 2A subunit concentrations were not found to be different in all groups statistically. Oxidative stress has been proposed to explain the biological side effect of experimental menopause. Melatonin prevents experimental menopause–induced oxidative stress to strengthen antioxidant vitamin and NMDAR 2A subunit concentrations in ovariectomized rats.

Keywords

Oxidative stress Melatonin Hippocampal NMDA receptor Brain Reproduction 

Notes

Acknowledgement

B. O. and M. N. formulated the present hypothesis and were responsible for writing the report. M. D., I. S. O., H. Y. K. and R. S. were responsible for data analyses. M. T. M. made critical revisions to the manuscript. The study was partially supported by the Scientific Research Project Unit of Suleyman Demirel University (BAP-2008).

References

  1. Cabrera J, Reiter R, Tan DX, Qi W, Saniz RM, Mayo JC, Garcia JJ, Kim SJ, El-Sokkary G (2000) Melatonin reduces oxidative neurotoxicity due to quinolinic acid: in vitro and in vivo findings. Neuropharmacology 39:507–514CrossRefPubMedGoogle Scholar
  2. Christen Y (2000) Oxidative stress and Alzheimer disease. Am J Clin Nutr 71:621S–629SPubMedGoogle Scholar
  3. Chung J, Wood JL (1971) Oxidation of thiocyanate to cyanide catalysed by hemoglobin. J Biol Chem 246:555–560PubMedGoogle Scholar
  4. Cyr M, Ghribi O, Thibault C, Morissette M, Landry M, Di Paolo T (2001a) Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA and AMPA receptors. Brain Res Brain Res Rev 37:153–161CrossRefPubMedGoogle Scholar
  5. Cyr M, Thibault C, Morissette M, Landry M, Di Paolo T (2001b) Estrogen-like activity of tamoxifen and raloxifene on NMDA receptor binding and expression of its subunits in rat brain. Neuropsychopharmacology 25:242–257CrossRefPubMedGoogle Scholar
  6. Desai ID (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147CrossRefPubMedGoogle Scholar
  7. Ekmekcioglu C (2006) Melatonin receptors in humans: biological role and clinical relevance Biomed Pharmacother 60:97–108Google Scholar
  8. Frei B, England L, Ames BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86:6377–6381CrossRefPubMedGoogle Scholar
  9. Gordon BK, Macrae IM, Carswell HVO (2005) Effects of 17β-oestradiol on cerebral ischaemic damage and lipid peroxidation. Brain Res 1036:155–162CrossRefPubMedGoogle Scholar
  10. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658CrossRefPubMedGoogle Scholar
  11. Irwin RW, Yao J, Hamilton RT, Cadenas E, Brinton RD, Nilsen J (2008) Progesterone and estrogen regulate oxidative metabolism in brain mitochondria. Endocrinology 149:3167–3175CrossRefPubMedGoogle Scholar
  12. Jagota SK, Dani HM (1982) A new colorimetric technique for the estimation of vitamin C using Folin phenol reagent. Anal Biochem 127:178–182CrossRefPubMedGoogle Scholar
  13. Kovacic P, Somanathan R (2008) Unifying mechanism for eye toxicity: electron transfer, reactive oxygen species, antioxidant benefits, cell signaling and cell membranes. Cell Membr Free Radic Res 2:56–69Google Scholar
  14. Köylü H, Mollaoglu H, Ozguner F, Naziroğlu M, Delibaş N (2006) Melatonin modulates 900 MHz microwave-induced lipid peroxidation changes in rat brain. Toxicol Ind Health 22:211–216CrossRefPubMedGoogle Scholar
  15. Kükner AŞ, Kükner A, Nazıroğlu M, Çolakoğlu N, Çelebi S, Yilmaz T, Aydemir O (2004) Protective effects of intraperitoneal vitamin C, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig. Cell Biochem Funct 22:299–305CrossRefPubMedGoogle Scholar
  16. Kume-Kick J, Ferris DC, Russo-Menna I, Rice MA (1996) Enhanced oxidative stress in female rat brain after gonadectomy. Brain Res 738:8–14CrossRefPubMedGoogle Scholar
  17. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958CrossRefPubMedGoogle Scholar
  18. Maharaj DS, Maharaj H, Daya S, Glass BD (2006) Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity. J Neurochem 96:78–81CrossRefPubMedGoogle Scholar
  19. Mollaoglu H, Topal T, Ozler M, Uysal B, Reiter RJ, Korkmaz A, Oter S (2007) Antioxidant effects of melatonin in rats during chronic exposure to hyperbaric oxygen. J Pineal Res 42:50–54CrossRefPubMedGoogle Scholar
  20. Mooradian AD (1993) Antioxidant properties of steroids. J Steroid Biochem Mol Biol 45:509–511CrossRefPubMedGoogle Scholar
  21. Nakamura Y, Tamura H, Kashida S, Takayama H, Yamagata Y, Karube A, Sugino N, Kato H (2001) Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res 30:29–33CrossRefPubMedGoogle Scholar
  22. Nazıroğlu M (2007a) Molecular mechanisms of vitamin E on intracellular signaling pathways in brain. In: Goth L (ed) Reactive oxygen species and diseases. Research Signpost Press, Kerala, India, pp 239–256Google Scholar
  23. Nazıroğlu M (2007b) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001CrossRefPubMedGoogle Scholar
  24. Nazıroğlu M, Şimşek M, Şimşek H, Aydilek N, Özcan Z, Atılgan R (2004) Effects of hormone replacement therapy, vitamin C and E supplementation on antioxidants levels, lipid profiles and glucose homeostasis in postmenopausal women with type 2 diabetes. Clin Chim Acta 344:63–71CrossRefPubMedGoogle Scholar
  25. Nazıroğlu M, Kutluhan S, Yilmaz M (2008) Selenium and topiramate modulate oxidative stress and Ca+2 -ATPase, EEG records in pentylentetrazol-induced brain seizures in rats. J Membr Biol 225:39–49CrossRefPubMedGoogle Scholar
  26. Pieri C, Marra M, Moroni F, Recchioni R, MarchesellI F (1994) Melatonin: a peroxyl radical scavenger more effective than vitamin E. Life Sci 55:PL271–PL276Google Scholar
  27. Placer ZA, Cushman L, Johnson BC (1966) Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359–364CrossRefPubMedGoogle Scholar
  28. Rayman MP (2009) Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta 1790:1533–1540PubMedGoogle Scholar
  29. Reiter RJ (1991) Melatonin: the chemical expression of darkness. Mol Cell Endocrinol 79:C153–C158CrossRefPubMedGoogle Scholar
  30. Rohr UD, Herold J (2002) Melatonin deficiencies in women. Maturitas 41 (Suppl 1):S85–S104Google Scholar
  31. Sedlak J, Lindsay RHC (1968) Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’s reagent. Anal Biochem 25:192–205CrossRefPubMedGoogle Scholar
  32. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones B, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J, Investigators WHIMS (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2651–2662CrossRefPubMedGoogle Scholar
  33. Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS (2008) Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 29:219–237CrossRefPubMedGoogle Scholar
  34. Sutcu R, Yonden Z, Yilmaz A, Delibas N (2006) Melatonin increases NMDA receptor subunits 2A and 2B concentrations in rat hippocampus. Mol Cell Biochem 283:101–105CrossRefPubMedGoogle Scholar
  35. Suzuki J, Katoh N (1990) A simple and cheap method for measuring vitamin A in cattle using only a spectrophotometer. Jpn J Vet Sci 52:1282–1284Google Scholar
  36. Tafti M, Ghyselinck NB (2007) Functional implication of the vitamin A signaling pathway in the brain. Arch Neurol 64:1706–1711CrossRefPubMedGoogle Scholar
  37. Tamura H, Nakamura Y, Narimatsu A, Yamagata Y, Takasaki A, Reiter RJ, Sugino N (2008) Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. J Pineal Res 45:101–105CrossRefPubMedGoogle Scholar
  38. Tan DX, Manchester LC, Teron MP, Flores LJ, Reiter RJ (2007) One molecule, many derivates: a never-ending interaction of melatonin with reactive oxygen and nitrogen? J Pineal Res 42:28–42CrossRefPubMedGoogle Scholar
  39. Vedder H, Anthes N, Stumm G, Würz C, Behl C, Krieg JC (1999) Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J Neurochem 72:2531–2538CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Müfide Dilek
    • 1
  • Mustafa Nazıroğlu
    • 2
    • 3
  • H. Baha Oral
    • 1
  • İ. Suat Övey
    • 2
  • Mustafa Küçükayaz
    • 2
  • M. Tamer Mungan
    • 1
  • H. Yusuf Kara
    • 4
  • Recep Sütçü
    • 4
  1. 1.Department of Gynecology, Medical FacultySuleyman Demirel UniversityIspartaTurkey
  2. 2.Department of Biophysics, Medical FacultySuleyman Demirel UniversityIspartaTurkey
  3. 3.Neuroscience Research CenterSuleyman Demirel UniversityIspartaTurkey
  4. 4.Department of Biochemistry, Medical FacultySuleyman Demirel UniversityIspartaTurkey

Personalised recommendations