Aysel GUVEN, Kezban Yıldız DALGINLI, Hacer ÇULHAOĞLU, Nergiz HUSEYİNOGLU, Selen İlhan ALP

Alzheimer Hastalığı Olan Hastalarda Kan MDA, GSH ve Nitrik Oksit Düzeylerinin Araştırılması

Amaç: Bu çalışmanın amacı Alzheimer hastalığı (AH) olan hastalarda kan malondialdehit (MDA), redükte Glutatyon (GSH) ve nitrik oksit (NO) seviyelerini belirlemektir. Materyal ve Metot: Çalışmaya Kars’ta yaşayan 65 ve 79 yaşları arasında 15 sağlıklı kişi ve 15 Alzheimer hastası dâhil edildi. Kafkas Üniversitesi Tıp Fakültesi Nöroloji Servisi’nde Alzheimer tanısı konan hastalardan kan örnekleri alınmadan önce Standart Mini Zihinsel Durum Muayenesi (SMMSE) ve Klinik Demans Derecesi uygulandı. Bir sonraki adımda eritrosit GSH ve serum MDA, NO seviyeleri belirlendi. Bulgular: Sağlıklı kişiler ile Alzheimer hasta grubu eritrosit GSH (p<0,05) ve serum MDA (p<0,01), NO (p<0,001) düzeyleri arasındaki fark istatistiksel olarak anlamlı bulundu. MMSE skorları kontrol grubundan anlamlı olarak düşük (p<0,001) bulundu. Sonuç: AH’ın lipid peroksidasyon oluşumuna yol açtığı ve bunun sonucu olarak AH’nın kanındaki MDA, GSH ve NO seviyelerini önemli ölçüde arttırdığı görülmüştür. Bu çalışma AH durumunda beynin artan oksidatif stresden etkilendiği teorisini desteklemektedir.

Anahtar Kelimeler:

Alzheimer, malondialdehit, glutatyon; lipit peroksidasyonu; nitrik oksit

Investigation of the Levels of Blood MDA, GSH and Nitric Oxide Levels in Patients with Probable Alzheimer’s Disease

PDF

___

1. Gilman S. Alzheimers disease. Perspect Biol Med. 1997;40:230-45.
2. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R et al. 1991. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572-80.
3. Law A, Gauthier S, Quirion R. Say NO to Alzheimer’s disease: the putative links between nitric oxide and dementia of the Alzheimer’s type. Brain Research Reviews 2001; 35: 73–96.
4. Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012; doi:10.1155/2012/428010.
5. Winslow BT, Onysko MK, Stob CM, Hazlewood KA. Treatment of Alzheimer disease. Am Fam Physician 2011; 83:1403-12.
6. Beal MF. Oxidative damage as an early marker of Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 2005;26:585-6.
7. Padurariu M, Ciobica A, Hritcu L, Stoica B, Bild W, Stefanescu C. Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett 2010; 469:6-10.
8. Padurariu M, Ciobica A, Lefter R, Serban IL, Stefanescu C, Chirita R. The oxidative stress hypothesis in Alzheimer’s disease. Psychiatr Danub 2013; 25:401-9.
9. Massaad CA: Neuronal and vascular oxidative stress inAlzheimer’s disease. Curr Neuropharmacol 2011; 9:662-73.
10. Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1987;1:358–64.
11. Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull 1993; 49:577–87.
12. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-Hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438
13. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009;7:65-74.
14. Salim S. Oxidative stress and the central nervous system. J Pharmacol Exp Ther 2017;360:201-5.
15. Greilberger J, Koidl C, Greilberger M, Lamprecht M, Schroecksnadel K, Leblhuber F et al. Malondialdehyde, carbonyl proteins and albümin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer’s disease. Free Radic Res 2008; 42:633-8.
16. Baldeiras I, Santana I, Proença MT, Garrucho MH, Pascoal R, Rodrigues A et al. Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer’s disease. J Alzheimers Dis. 2008;15:117-28.
17. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997; 82:291-5.
18. Shukla V, Mishra SK, Pant HC. Oxidative stress in neurodegeneration. Adv Pharmacol Sci 2011; 572634.
19. Pocernich CB., Butterfield DA. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochimica et Biophysica Acta 2012; 1812:625-30.
20. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on various uses of N-Acetyl Cysteine. Cell J. 2017;19: 11-17.
21. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying information in neurodegeneration, Cell. 2010;140:918-34.
22. Huang WJ, Zhang X and Chen WW. Role of oxidative stress in Alzheimer’s disease (Review) Biomedical Reports 2016; 4: 519-22.
23. Spiers J G, Cortina Chen HJ, Bourgognon JM, Steinert JR. Dysregulation of stress systems and nitric oxide signaling underlies neuronal dysfunction in Alzheimer’s disease. Free Radical Biology and Medicine 2019; 134: 468-83.
24. Picón-Pagès P, Garcia-Buendia J, Muñoz F J. Functions and dysfunctions of nitric oxide in brain. BBA-Molecular Basis of Disease 2019; 1865:1949-67.
25. Venturelli M. The Role of nitric oxide on vascular dysfunction during aging and Alzheimer’s disease. In: Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders 2019; 221-228.
26. Berg L. Clinical dementia rating. Br J Psychiatry 1984;145:339.
27. Placer ZA, Cushman LL, Johson BC. Estimation of Product of Lipid Peroxidation (Malonyl Dialdehyde) In Biochemical Systems. Anal Biochem 1966;16: 359-64.
28. Miranda KM, Espey MG, Wink DA. A Rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62-71.
29. Sedlak J, Lindsay RH. Estimation of total protein-bound and non-protein sülfhdryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192-205.
30. Lovell MA, Markesbery WR. Oxidative damage in mild cognitive impairment and early Alzheimer’s disease. J Neurosci Res. 2007;85:3036–40.
31. Montine TJ, Neely MD, Quinn JF, Beal FM, Markesbery WR, Roberts LJ et al. Lipid peroxidation in aging brain and Alzheimer’s disease. Free Radic Biol Med 2002;33:620-6.
32. Butterfield DA, Bader Lange ML, Sultana R. Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease, Biochim. Biophys. Acta 2010;1801:924-9.
33. Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease, Biochim Biophys Acta 2014;1842:1240-7.
34. Cheignona C, Tomasa M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology 2018;14:450-64.
35. Giavarotti L, Simon KA, Azzalis LA, Fonseca FLA, Lima AF, Freitas MCV et al. Mild systemic oxidative stress in the subclinical stage of Alzheimer’s disease. Oxidative Med Cell Longev 2013;609019.
36. Peña-Bautista C, Vigor C, Galano JM, Oger C, Durand T, Ferrer I et al. Plasma lipid peroxidation biomarkers for early and noninvasive Alzheimer disease detection. Free Radic Biol Med 2018;124:388-94.
37. Kheradmand E, Moghaddam AH, Zare M. Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer’s disease. Biomedicine Pharmacotherapy 2018:97;1096-1101.
38. Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, et al. A randomized placebo controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis 2014;38:111–120.
39. Yuan L, Liu J, Ma W, Dong L, Wang W, Che R et al. Dietary pattern and antioxidants in plasma and erythrocyte in patients with mild cognitive impairment from China. Nutrition 2016;32:193-8.
40. Luo Y, Roth GS. The roles of dopamine oxidative stress and dopamine receptor signaling in aging and age-related neurodegeneration. Antioxidants Redox Signaling 2004; doi. org/10.1089/15230860050192224
41. Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 2006;1:3159-65.
42. Tietz F. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione:application to mammalian blood and other tissues. Analytical Biochemistry 1969;27:502-22.
43. Martensson J. Method for determination of free and total glutathione and γ-glutamylcysteine concentrations in human leukocytes and plasma. Journal of chromatography 1987;420:152-7.
44. Mopper K. Trace determination of biological thiols by liquid chromatography and precolumn fluorometric labeling with o-phthalaldehyde. Anal Chem 1984;56:2557-60. 45. Akkaya C, Sahin Yavuzer S, Yavuzer H, Erkol G, Bozluolcay M, Dinçer Y. DNA damage, DNA susceptibility to oxidation and glutathione redox status in patients with Alzheimer’s disease treated with and without memantine. J Neurol Sci 2017;378:158-162.
46. Mandal PK, Saharan S, Tripathi M, Murari G. Brain glutathione levels-a novel biomarker for mild cognitive impairment and Alzheimer’s disease. Biological Psychiatry 2015;78:702-10.
47. Güzel S, Yıldız Ö, Ünal A, Kızıler AR, Gülyaşar T, Celik Güzel E, et al. Doublecortin-like kinase 1 levels and oxidant status in Alzheimer’s disease. Cukurova Medical Journal 2017;42:687-693.
48. Venturelli M. The role of nitric oxide on vascular dysfunction during aging and Alzheimer’s disease. Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders 2019;221-228.
49. Lourenço CF, Ledo A, Barbosa RM, Laranjinha J: Neurovascular uncoupling in the triple transgenic model of Alzheimer’s disease: Impaired cerebral blood flow response to neuronal-derived nitric oxide signaling. Experimental Neurology 2017;291:36-43.
50. Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta 2000;1502:139-44.
51. Markesbery WR. Oxidative Stres Hypothesis in AD. Free Radic Biol Med 1997;23:134-147.
52. Wong A, Lüth HJ, Deuther-Conrad W, Dukic-Stefanovic S, Gasic-Milenkovic J, Arendt T et al. Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease. Brain Research 2001;920:32–40.
53. Fernández -Vizarra P, Fernández AP, Castro-Blanco S, Encinas JM, Serrano J, Bentura MLet al. Expression of nitric oxide system in clinically evaluated cases of Alzheimer’s disease. Neurobiol Dis 2004;15:287-305.
54. Brossard B. 4-Objectifying dementia: The use of the minimental state exam in medical research and practice. Psychiatry Science and Society 2018;127-154.
55. Tzimourta KD, Afrantou T, Ioannidis P, Karatzikou M, Tzallas AT et al. Analysis of electroencephalographic signals complexity regarding Alzheimer’s Disease. Computers and Electrical Engineering 2019;76:198-212.
56. Santabarbara J, Gracia-Rebled AC, Lopez-Anton R, Tomas C, Lobo E, Marcos G, et al. The effect of occupation type on risk of Alzheimer’s disease in men and women. 2019;126:61-8.