Ratlarda Amiloid Beta1-42 İle Oluşturulan Deneysel Alzheimer Modelinde Tiyol Disülfit Homeostazisi

Yıl 2020, Cilt: 10 Sayı: 3, 343 - 347, 21.09.2020

Ayhan Çetinkaya

https://doi.org/10.33631/duzcesbed.698151

Cited By: 1

Öz

Amaç: Bu çalışmanın amacı, amiloid beta 1-42 enjekte edilerek Alzheimer modeli oluşturulan ratlarda, oksidan ve antioksidan dengenin yeni bir oksidatif stres belirteci olan dinamik tiyol disülphide homeostazisinin, serum total tiyol, natif tiyol, ve disülfit seviyelerinin araştırılması ve disulfit/total tiyol ve disulfit/natif tiyol oranlarının değerlendirilmesidir.
Gereç ve Yöntemler: Bu deneysel çalışma 28 rat üzerinde gerçekleştirildi. Denekler her grupta 14 adet olacak şekilde, Alzheimer ve kontrol grubu olarak ikiye ayrıldı. Amiloid beta 1-42, enjeksiyon için bir hafta inkubatörde bekletilerek toksititesi artırıldı. Alzheimer grubunda yer alan hayvanlara bilateral 4 µl amiloid beta 1-42 enjekte edilerek deneysel Alzheimer modeli oluşturuldu. 10 gün beklenildikten sonra tüm hayvanlardan 90/10 mg/kg ksilazine/ketamin anestezisi altında intra kardiyak alınan kan numuneleri ile laboratuvarda TDH parametreleri çalışıldı (nativ tiyol, total tiyol, disülfid, disulfit/total tiyol oranı ve disulfit/natif tiyol oranı) ve bu parametreler gruplar arasında karşılaştırıldı.
Bulgular: Çalışma ve kontrol grupları karşılaştırıldığında, serum total tiyol düzeyleri (469,85±30,65 ve 558,00±23,46) ile serum disülfid düzeyleri (182,57±15,74 ve 224,85±11,95), alzheimer modeli oluşturulan grupta kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde azalma görülürken (p<0,05) serum natif tiyol düzeylerinde (104,71±8,17 ve 108,28±9,71) ise anlamlı bir fark bulunamamıştır(p>0,05).
Sonuç: İlgili çalışma, deneysel olarak oluşturulan Alzheimer modellemelerinde serumda dinamik tiyol-disülfid homeostazını değerlendiren ilk araştırmadır. Çalışmamızın sonuçları TDH’ın deneysel alzheimer modellemelerinde, oksidatif stres mekanizmalarının değerlendirilmesinde ucuz ve kolay yeni bir markerı olabileceğini düşündürmektedir.

Anahtar Kelimeler

Homeostaz, oksidatif stres, alzheimer hastalığı, amiloid beta-peptidler, hayvan deneyleri

Destekleyen Kurum

Bolu Abant İzzet Baysal Üniversitesi

Proje Numarası

2018.08.02.1393

Thiol Disulphide Homeostasis in Amyloid Beta 1-42 Induced Experimental Alzheimer's Model

Öz

Aim: The aim of the present study was to investigate the dynamic thiol disulphide homeostasis as a novel oxidative stress marker of oxidant and antioxidant balance, and the serum levels of total thiol, native thiol, and disulfide as well as disulphide/total thiol and disulphide/native thiol ratios in rats with Alzheimer's model induced by amyloid beta 1-42 administration.
Material and Methods: This experimental study was carried out on 14 rats. The animals were randomly divided into two groups: Alzheimer's group (n = 14) and the control group (n = 14). The amyloid beta 1-42 was kept in the incubator for a week to increase its toxicity. Animals in the experimental groups were bilaterally administered 4 µl amyloid beta 1-42. Following 10 days of waiting, all animals were anesthetized and intra-cardiac blood samples were collected for the analyses of native thiol, total thiol, disulfide, disulphite / total thiol ratio and disulphite / native thiol ratio.
Results: We detected that serum total thiol levels were 469.85±30.65 and 558.00±23.46 (p<0.05), serum native thiol levels were 104.71±8.17 and 108.28±9.71 (p>0.05) and serum disulphide levels were 182.57±15.74 and 224.85±11.95 (p<0.05) in the study and control groups, respectively.
Conclusion: To the best of our knowledge, the current study is the first report in the literature evaluating dynamic thiol disulphide homeostasis in experimentally induced Alzheimer's model. The results of the present study suggested that thiol disulphide homeostasis can be an inexpensive, easy and novel marker for the evaluation of oxidative stress mechanisms in experimentally induced Alzheimer's model.

Anahtar Kelimeler

Homeostasis, oxidative stress, alzheimer disease, amyloid beta-peptides, animal experimentation

Proje Numarası

2018.08.02.1393

Kaynakça

• Association AS. 2016 Alzheimer's disease facts and figures. Alzheimer's & Dementia. 2016; 12(4): 459-509.
• Bettens K, Sleegers K, Van Broeckhoven C. Current status on Alzheimer disease molecular genetics: from past, to present, to future. Hum Mol Genet. 2010; 19(R1): 4‐11.
• Nikolac Perkovic M, Pivac N. Genetic markers of Alzheimer's disease. Adv Exp Med Biol. 2019; 1192: 27-52.
• Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer's disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019; 2019(14): 5541-54.
• Goedert M, Spillantini MG. A century of Alzheimer's disease. Science. 2006; 314(5800): 777-81.
• Reddy VP, Zhu X, Perry G, Smith MA. Oxidative stress in diabetes and Alzheimer's disease. J Alzheimers Dis. 2009; 16(4): 763‐74.
• Tobore TO. On the central role of mitochondria dysfunction and oxidative stress in Alzheimer's disease. Neurol Sci. 2019; 40(8): 1527-40.
• Zhang H, Forman HJ. 4-hydroxynonenal-mediated signaling and aging. Free Radic Biol Med. 2017; 111: 219-25.
• Moldogazieva NT, Mokhosoev IM, Mel'nikova TI, Porozov YB, Terentiev AA. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid Med Cell Longev. 2019; 2019: 3085756.
• Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017; 482(3): 419-25.
• Puspita L, Chung SY, Shim JW. Oxidative stress and cellular pathologies in Parkinson's disease. Mol Brain. 2017; 10(1): 53.
• da Fonsêca DV, da Silva Maia Bezerra Filho C, Lima TC, de Almeida RN, de Sousa DP. Anticonvulsant essential oils and their relationship with oxidative stress in epilepsy. Biomolecules. 2019; 9(12): 1-40.
• Padureanu R, Albu CV, Mititelu RR, Bacanoiu MV, Docea AO, Calina D, et al. Oxidative stress and inflammation interdependence in Multiple sclerosis. J Clin Med. 2019; 8(11): 1-11.
• Sawa A, Sedlak TW. Oxidative stress and inflammation in schizophrenia. Schizophr Res. 2016; 176(1): 1-2.
• Tripathi GM, Kalita J, Misra UK. A study of oxidative stress in migraine with special reference to prophylactic therapy. Int J Neurosci. 2018; 128(4): 318-24.
• Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clinical Biochemistry. 2014; 47(18): 326-32.
• Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009; 47(10): 1329-38.
• Sabens EA, Distler AM, Mieyal JJ. Levodopa deactivates enzymes that regulate thiol−disulfide homeostasis and promotes neuronal cell death: Implications for therapy of parkinson’s disease. Biochemistry. 2010; 49(12): 2715-24.
• Topcuoglu C, Bakirhan A, Yilmaz FM, Neselioglu S, Erel O, Sahiner SY. Thiol/disulfide homeostasis in untreated schizophrenia patients. Psychiatry Research. 2017; 251: 212-6.
• Erzin G, Kotan VO, Topçuoğlu C, Özkaya G, Erel Ö, Yüksel RN, et al. Thiol/disulphide homeostasis in bipolar disorder. Psychiatry Research. 2018; 261: 237-42.
• Jean YY, Baleriola J, Fà M, Hengst U, Troy CM. Stereotaxic infusion of oligomeric amyloid-beta into the mouse hippocampus. J Vis Exp. 2015; 100: e52805.
• Facchinetti R, Bronzuoli MR, Scuderi C. An animal model of Alzheimer disease based on the intrahippocampal injection of amyloid β-peptide (1–42). Methods Mol Biol. 2018; 1727: 343-52.
• Sugawara T, Kawase M, Lewén A, Noshita N, Gasche Y, Fujimura M, et al. Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model. Brain Res. 2000; 877 (2): 281-7.
• Lee JH, Shin HK, Park SY, Kim CD, Lee WS, Hong KW. Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats. Exp Neurol. 2009; 215(1): 87-94.
• Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997; 23(1): 134-47. McBean GJ, Aslan M, Griffiths HR, Torrão RC. Thiol redox homeostasis in neurodegenerative disease. Redox Biol. 2015; 5: 186-94.
• Xiao Z, La Fontaine S, Bush AI, Wedd AG. Molecular mechanisms of glutaredoxin enzymes: Versatile hubs for thiol-disulfide exchange between protein thiols and glutathione. J Mol Biol. 2019; 431(2): 158-77.
• Coşkun C, Emre HÖ, Gümüş A, Uzun S, Karadağ S, Behlül A, ve ark. Diyabetik ve diyabetik olmayan kronik böbrek yetmezliğinde dinamik tiyol disülfit homeostazı ve ileri protein oksidasyon ürünleri (AOPPs). Deneysel Tıp Araştırma Enstitüsü Dergisi. 2016; 6(12): 1-9.
• Büyükgüzel E, Akın R. Redoksa duyarlı sinyal iletiminde reaktif oksijen türlerinin (ROT) rolü. Karaelmas Science & Engineering Journal. 2014; 4(2); 70-81.
• Zecca L, Zucca FA, Wilms H, Sulzer D. Neuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics. Trends Neurosci. 2003; 26(11): 578-80.
• Gumusyayla S, Vural G, Bektas H, Deniz O, Neselioglu S, Erel O. A novel oxidative stress marker in patients with Alzheimer’s disease: dynamic thiol–disulphide homeostasis. Acta Neuropsychiatr. 2016; 28(6): 315-20.
• Samineni S, Parvataneni S, Kelly C, Gangur V, Karmaus W, Brooks K. Optimization, comparison, and application of colorimetric vs. chemiluminescence based ındirect sandwich ELISA for measurement of human IL‐23. J Immunoassay Immunochem. 2006; 27(2): 183-93.