Ratlarda 3-Asetilpyridin ile Oluşturulan Ataksi Modelinde Aposinin'in İskemi Modifiye Albümin (İMA) Düzeyleri Üzerindeki Etkisi

Abstract

Serebellar ataksi koordinasyon bozukluğuna sebep olan nörodejenereatif bir hastalıktır. Bunun gibi nörodejeneratif hastalıklarda apocynin (APO) gibi bileşiklerin tedavi edici rolü bulunmaktadır. Yapılan çalışmanın amacı, 3-asetilpyridin (3-AP) ile oluşturulan serebellar ataksi modelinde APO tedavisinin iskemi modifiye albümin (İMA) seviyesi üzerindeki etkisini incelemektir. Çalışmada, 200–250 gr ağırlığında Sprague-Dawley cinsi, 5-6 haftalık erkek ratlar kullanıldı. Ratlar, Kontrol grubu, 3-AP grubu, 3-AP + APO grubu ve APO grubu olmak üzere dört gruba ayrıldı. 3-AP uygulaması ile ratlarda serebellar ataksi modeli oluşturuldu ve tedavi için APO uygulandı. Deney sonunda anestezi altında dekapitasyon gerçekleştirilerek alınan beyin dokularında İMA seviyeleri ölçüldü. Tüm gruplara göre 3-AP uygulanan ratlarda İMA düzeylerinde istatistiksel olarak anlamlı artış saptanırken, APO uygulanan ratlarda İMA seviyelerinde istatistiksel olarak anlamlı azalış tespit edildi (p<0.001). Son yıllarda biomarker olarak İMA düzeylerinin kullanılabilirliği yönünde birçok çalışma olsada yapılan literatür taramalarında APO’nun 3-AP uygulaması sonucu serebellar ataksi gibi nörodejeneratif hastalıklarda terapötik bir bileşik olarak kullanılabileceğine yönelik beyin İMA düzeylerine bakılan herhangi bir literature rastlanılmadığı için yapılan çalışma literatüre öncü çalışma olarak sunulmuştur. Elde edilen bulgular yapılacak çalışmalar için ışık tutar niteliktedir.

Keywords

• Antioksidan
• aposinin
• ataksi
• beyin
• İMA

The Effect of Apocynin on Ischemia Modified Albumin (IMA) Levels in the Ataxia Model Induced with 3-Acetylpyridine in Rats

Abstract

Cerebellar ataxia is a neurodegenerative disease that causes coordination disorder. In such neurodegenerative diseases, compounds such as apocynin (APO) have a therapeutic role. The aim of this study is to examine the effect of APO treatment on ischemia modified albumin (IMA) level in the cerebellar ataxia model induced by 3-acetylpyridine (3-AP). In the study, 5–6-week-old male Sprague-Dawley rats weighing 200-250 grams were used. Rats were divided into four groups: Control group (K), 3- 3-AP group, 3-AP + APO, and APO group. A cerebellar ataxia model was induced in rats using 3-AP administration, and APO was administered as a treatment. At the end of the experiment, decapitation was performed under anesthesia, and IMA levels were measured in the brain tissues obtained. In rats administered with 3-AP, there was a statistically significant increase in IMA levels compared to all groups, whereas rats treated with APO showed a statistically significant decrease in IMA levels (p<0.001). Although many studies in recent years have investigated the usability of IMA levels as biomarkers, literature searches did not reveal any studies examining the therapeutic potential of APO in neurodegenerative diseases like cerebellar ataxia induced by 3-AP, in terms of brain IMA levels. Therefore, this study is presented as a pioneering contribution to the literature. The findings obtained shed light on future research.

Keywords

• Antioxidant
• apocynin
• ataxia
• brain
• IMA

References

1. Abo Saleh, A., Marouf, B., & Zrieki, A. (2023). Ischemia Modified Albumin (Ima): A Novel Biomarker For The Diagnosis Of Acute Coronary Syndrome. Bulletin of Pharmaceutical Sciences Assiut University, 46(1), 473-481. doi: 10.21608/bfsa.2023.301186
2. Aghighi, Z., Ghorbani, Z., Moghaddam, M. H., Fathi, M., Abdollahifar, M.-A., Soleimani, M., Karimzadeh, F., Rasoolijazi, H., & Aliaghaei, A. (2022). Melittin ameliorates motor function and prevents autophagy-induced cell death and astrogliosis in rat models of cerebellar ataxia induced by 3-acetylpyridine. Neuropeptides, 96, 102295. https://doi.org/10.1016/j.npep.2022.102295
3. Ajayi, A., Yu, X., Lindberg, S., Langel, Ü., & Ström, A.-L. (2012). Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model. BMC Neuroscience, 13(1), 86. https://doi.org/10.1186/1471-2202-13-86
4. Arroyo, V., García-Martinez, R., & Salvatella, X. (2014). Human serum albumin, systemic inflammation, and cirrhosis. Journal of Hepatology, 61(2), 396-407. https://doi.org/10.1016/j.jhep.2014.04.012
5. Bar–Or, D., Lau, E., & Winkler, J. V. (2000). A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. The Journal of Emergency Medicine, 19(4), 311-315. https://doi.org/10.1016/S0736-4679(00)00255-9
6. Canakci, E., Karatas, A., Dereli, S., Kaya, Y., Bayrak, T., Coskun, I., Altınbaş, A., & Cebeci, Z. (2022). Association between ischemia modified albumin and myeloperoxidase levels with epicardial adipose tissue thickness in acute kidney injury in intensive care patients. Firat Medical Journal, 27(4), 269–276.
7. Cao, B.-B., Zhang, X.-X., Du, C.-Y., Liu, Z., Qiu, Y.-H., & Peng, Y.-P. (2020). TGF-β1 Provides Neuroprotection via Inhibition of Microglial Activation in 3-Acetylpyridine-Induced Cerebellar Ataxia Model Rats. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.00187
8. Claassen D. O. (2022). Multiple System Atrophy. Continuum (Minneapolis, Minn.), 28(5), 1350–1363. https://doi.org/10.1212/CON.0000000000001154

9. Demirci, B., Karakılıç, M. E., Coşkun, A., Yel, C., Uyanık, S. A., Ünal, K., Başpınar, İ., Çaltılı, Ç., & İnan, S. (2021). The Brain Ischemic Volume Correlation with the Ischemic Modified Albumin Level. Bagcilar Medical Bulletin, 6(1), 26-31. https://doi.org/10.4274/BMB.galenos.2020.10.068
10. Ghorbani, Z., Abdollahifar, M. A., Vakili, K., Moghaddam, M. H., Mehdizadeh, M., Marzban, H., Rasoolijazi, H., & Aliaghaei, A. (2022). Melittin administration ameliorates motor function, prevents apoptotic cell death and protects Purkinje neurons in the rat model of cerebellar ataxia induced by 3-Acetylpyridine. Toxicon, 205, 57-66. https://doi.org/10.1016/j.toxicon.2021.11.008
11. Jaques, C. S., Escorcio-Bezerra, M. L., Pedroso, J. L., & Barsottini, O. G. P. (2022). The Intersection Between Cerebellar Ataxia and Neuropathy: a Proposed Classification and a Diagnostic Approach. Cerebellum (London, England), 21(3), 497–513. https://doi.org/10.1007/s12311-021-01275-2
12. Karakılıç, E., Çelikel, E., Uysal, P. I., Topçuoğlu, C., Turhan, T., & Özakın, E. (2023). Diagnostic Value of Ischemia-Modified Albumin as a Biomarker in Patients with Peripheral Vertigo at Emergency Department of State Hospital in Ankara: A Cross-Sectional Study. Nigerian journal of clinical practice, 26(12), 1779–1783. https://doi.org/10.4103/njcp.njcp_1862_21
13. Kennelly, P. J., Botham, K. M., McGuinness, O., Rodwell, V. W., & Weil, P. A. (2023). Harper’s Illustrated Biochemistry (32nd ed.). McGraw Hill LLC.
14. Lastres-Becker, I., Rüb, U., & Auburger, G. (2008). Spinocerebellar ataxia 2 (SCA2). The Cerebellum, 7(2), 115-124. https://doi.org/10.1007/s12311-008-0019-y
15. Liu, P., Cui, L., Liu, B., Liu, W., Hayashi, T., Mizuno, K., Hattori, S., Ushiki-Kaku, Y., Onodera, S., & Ikejima, T. (2020). Silibinin ameliorates STZ-induced impairment of memory and learning by up- regulating insulin signaling pathway and attenuating apoptosis. Physiology & Behavior, 213, 112689. https://doi.org/10.1016/j.physbeh.2019.112689
16. Manto, M., & Marmolino, D. (2009). Cerebellar ataxias. Current Opinion in Neurology, 22(4), 419-429. https://doi.org/10.1097/WCO.0b013e32832b9897
17. Mazzonetto, P. C., Ariza, C. B., Ocanha, S. G., de Souza, T. A., Ko, G. M., Menck, C. F. M., Massironi, S. M. G., & Porcionatto, M. A. (2019). Mutation in NADPH oxidase 3 (NOX3) impairs SHH signaling and increases cerebellar neural stem/progenitor cell proliferation. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1865(6), 1502-1515. https://doi.org/10.1016/j.bbadis.2019.02.022
18. O'Malley J. A. (2022). Diagnosing Common Movement Disorders in Children. Continuum (Minneapolis, Minn.), 28(5), 1476–1519. https://doi.org/10.1212/CON.0000000000001187
19. Ranjbar, H., Soti, M., Janahmadi, M., Kohlmeier, K. A., Sheibani, V., Ahmadi-Zeidabadi, M., & Shabani, M. (2022). Modulation of the CB1 cannabinoid receptor has potential therapeutic utility in the 3-acetylpyridine cerebellar ataxia rat model. Experimental Brain Research, 240(9), 2339-2348. https://doi.org/10.1007/s00221-022-06415-6
20. Rosenthal L. S. (2022). Neurodegenerative Cerebellar Ataxia. Continuum (Minneapolis, Minn.), 28(5), 1409–1434. https://doi.org/10.1212/CON.0000000000001180
21. Saeidikhoo, S., Ezi, S., Khatmi, A., Aghajanpour, F., Soltani, R., Abdollahifar, M. A., Jahanian, A., & Aliaghaei, A. (2020). Effect of Sertoli Cell Transplantation on Reducing Neuroinflammation-Induced Necroptosis and Improving Motor Coordination in the Rat Model of Cerebellar Ataxia Induced by 3-Acetylpyridine. Journal of Molecular Neuroscience, 70(7), 1153-1163. https://doi.org/10.1007/s12031-020-01522-x
22. Sbarouni, E., Georgiadou, P., & Voudris, V. (2011). Ischemia modified albumin changes - review and clinical implications. Clinical chemistry and laboratory medicine, 49(2), 177–184. https://doi.org/10.1515/CCLM.2011.037
23. Shevtsova, A., Gordiienko, I., Tkachenko, V., & Ushakova, G. (2021). Ischemia-Modified Albumin: Origins and Clinical Implications. Disease Markers, 2021, 1-18. https://doi.org/10.1155/2021/9945424
24. Simonyi, A., Serfozo, P., Lehmidi, T. M., Cui, J., Gu, Z., Lubahn, D. B., Sun, A. Y., & Sun, G. Y. (2012). The neuroprotective effects of apocynin. Frontiers in bioscience (Elite edition), 4(6), 2183–2193. https://doi.org/10.2741/535
25. Tahtacı, M., Başaran, M., Köseoğlu, H., Yildirim, F., Ahmedova, P., Akin, F., Alişik, M., Bolat, A., Kivrakoğlu, F., Erel, Ö., & Ersoy, O. (2019). Karaciğer fibrozisli olgularda serum iskemi modifiye albüminin değerlendirilmesi. Akademik Gastroenteroloji Dergisi, 19(1), 21-24. https://doi.org/10.17941/agd.723299
26. Torres-Ramos, Y., Montoya-Estrada, A., Cisneros, B., Tercero-Pérez, K., León-Reyes, G., Leyva-García, N., Hernández-Hernández, O., & Magaña, J. J. (2018). Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity. The Cerebellum, 17(5), 601-609. https://doi.org/10.1007/s12311-018-0947-0
27. van der Heijden, M. E., & Sillitoe, R. V. (2021). Interactions Between Purkinje Cells and Granule Cells Coordinate the Development of Functional Cerebellar Circuits. Neuroscience, 462, 4-21. https://doi.org/10.1016/j.neuroscience.2020.06.010
28. Wecker, L., Marrero-Rosado, B., Engberg, M. E., Johns, B. E., & Philpot, R. M. (2017). 3-Acetylpyridine neurotoxicity in mice. NeuroToxicology, 58, 143-152. https://doi.org/10.1016/j.neuro.2016.11.010
29. Xiang, J., He, L., Pen, T., & Wei, S. (2023). Ischemia modified albumin can act as an independent predictor of inhospital mortality in patients with acute aortic dissection. Scientific reports, 13(1), 343. https://doi.org/10.1038/s41598-023-27659-4
30. Yu, J., Weiwer, M., Linhardt, R., & Dordick, J. (2008). The Role of the Methoxyphenol Apocynin, a Vascular NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the Potential Treatment of Cardiovascular Diseases. Current Vascular Pharmacology, 6(3), 204-217. https://doi.org/10.2174/157016108784911984