Parkinson modelinde borik asit ve kuersetin kombinasyonu’nun oksidatif stres/ bilişsel fonksiyon üzerine etkisi

Öz

Parkinson hastalığı (PH), beyinde dopaminerjik nöronlara etki eden önemli bir nörodejeneratif bozukluktur. Kuersetin, doğrudan radikal temizleme aktiviteleri ve antioksidatif enzimlerin indüksiyonu ile tüm flavonoidler arasında en güçlü antioksidanlardan biridir. Yapılan çalışmalarda Borik asidin kalsiyum, vitamin D ve magnezyum ile etkileşime girerek organlar için yararlı etkilere sahip olduğu gösterilmiştir. Çalışmamızda 3 aylık Wistar-albino erkek sıçan kullandık, deney grupları 8 gruba (n=7) ayrıldı ve beyin doku örneklerinde Glutatyon (GSH) ve Malondialdehit (MDA) seviyeleri manuel olarak belirlendi. Aynı zamanda Total Antioksidan Durumu (TAS) ticari kit kullanılarak tayin edildi. Sıçanların bilişsel işlevlerini değerlendirmek için Lokomotor Aktivite ve Nesne Tanıma testleri uygulandı. İstatistiksel analizlerde GraphPad Prism 9 versiyonu kullanıldı. Değerler, tek yönlü ANOVA ile istatistiksel olarak analiz edildi, gruplar arasındaki farklılıklar Uncorrected Fisher's LSD testleri kullanılarak belirlendi. p < 0,05 istatistiksel olarak anlamlı kabul edildi. Buna göre çalışmamızın sonucunda Kuersetin ve Borik asidin antioksidan kapasite üzerine olumlu etkiler yaparak TAS seviyelerinde etkili olduğu gösterilmiştir. Çalışmamızda BA'nın PH patogenezini önleyerek oksidan-antioksidan dengeyi olumlu yönde etkileyeceği görüşündeyiz. Parkinson's disease (PD) is a one of the important neurodegenerative disorders that affect dopaminergic neurons in the brain. Quercetin is one of the most potent antioxidants among all flavonoids, with direct radical scavenging activities and induction of antioxidative enzymes. Studies have shown that boric acid is essential for the activity of brain functions. We also used 3-month-old Wistar-albino male rats in our study, the experimental groups were divided into 8 groups (n=7) and Glutathione (GSH) and Malondialdehyde (MDA) levels were determined manually in brain tissue samples. Also, Total Antioxidant Status (TAS) was determined using a commercial kit. Locomotor Activity and Object Recognition tests were applied to evaluate the cognitive functions of the rats. GraphPad Prism 9 version was used for statistical analysis. Values were statistically analyzed by one-way ANOVA, differences between groups were determined using Uncorrected Fisher's LSD tests. p < 0.05 was considered statistically significant. In our study, we think that BA will positively affect the oxidant-antioxidant balance by preventing the pathogenesis of PD.

Anahtar Kelimeler

• Parkinson,
• Rotenon,
• Borik asit,
• Kuersetin,
• Oksidatif stres

Effect of boric acid and quercetin combination on oxidative stress/ cognitive function in parkinson model

Öz

Parkinson's disease (PD) is a one of the important neurodegenerative disorders that affect dopaminergic neurons in the brain. Quercetin is one of the most potent antioxidants among all flavonoids, with direct radical scavenging activities and induction of antioxidative enzymes. Studies have shown that boric acid is essential for the activity of brain functions. We also used 3-month-old Wistar-albino male rats in our study, the experimental groups were divided into 8 groups (n=7) and Glutathione (GSH) and Malondialdehyde (MDA) levels were determined manually in brain tissue samples. Also, Total Antioxidant Status (TAS) was determined using a commercial kit. Locomotor Activity and Object Recognition tests were applied to evaluate the cognitive functions of the rats. GraphPad Prism 9 version was used for statistical analysis. Values were statistically analyzed by one-way ANOVA, differences between groups were determined using Uncorrected Fisher's LSD tests. p < 0.05 was considered statistically significant. In our study, we think that BA will positively affect the oxidant-antioxidant balance by preventing the pathogenesis of PD.

Anahtar Kelimeler

• Parkinson,
• Rotenone,
• Boric acid,
• Quercetin,
• Oxidative stress

Kaynakça

1. Sankhla, C. S. (2017). Oxidative stress and parkinson'sdisease. Neurology India, 65(2), 269-270. https://doi. org/10.4103/0028-3886.201842.
2. Radhakrishnan, D. M., & Goyal, V., (2018). Parkinson's disease: A review. All India Institute of Medical Sciences, 66(7), 26-35. https://doi.org/10.4103/0028-3886.226451.
3. Rocha, E. M., De Miranda, B., & Sanders, L. H. (2018). Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in parkinson's disease. Neurobiology of Disease, 109(Pt B), 249-257. https://doi.org/10.1016/j.nbd.2017.04.004.
4. Alikatte, K., Palle, S., Rajendra Kumar, J., & Pathakala, N. (2021). Fisetin improved rotenone-induced behavioral deficits, oxidative changes, and mitochondrial dysfunctions in rat model of parkinson's disease. Journal of Dietary Supplements. 18(1), 57-71. https://doi.org/10. 1080/19390211.2019.1710646.
5. Xu, Q., Yang, S., Wu, F., Lin, Y., Zhong, J., Tang, L., … & Cai, J. (2020). Congrong shujing granule-induced GRP78 expression reduced endoplasmic reticulum stress and neuronal apoptosis in the midbrain in a parkinson's disease rat model. Evidence-Based Complementary and Alternative Medicine: eCAM, 4796236, 1-12. https://doi.org/10.1155/2020/4796236.
6. Pajares, M. I Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020). Inflammation in parkinson's disease: Mechanisms and therapeutic implications. Cells, 9(7), 1687. https://doi.org/10.3390/cells9071687.
7. Serdaroglu Kasikci, E., (2018). Evoluation of longterm quercetin administration on age related oxidative stress induced by D-galactose in rats. Fresenious Environmental Bulletin, 27(11), 7781-7786. https://doi. org/11/2018 pages 7781-7786.
8. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, ... & Bitto, A. (2017). Oxidative Stress: Harms and benefits for human health. Oxidative Medicine and Cellular Longevity, 8416763, 1-13. https:// doi.org/10.1155/2017/8416763.

9. Smeyne, M., & Smeyne, R. J., (2013). Glutathione metabolism and parkinson's disease. Free Radical of Biological Medicine, 62, 13-25. https://doi.org/10.1016/j.freeradbiomed.2013.05.001.
10. Coban, F. K., Ince, S., Kucukkurt, I., Demirel, H. H., & Hazman, O. (2015). Boron attenuates malathioninduced oxidative stress and acetylcholinesterase inhibition in rats. Drug and Chemical Toxicology, 38, 391-399. https://doi.org/10.3109/01480545.2014.974109.
11. Sinha, N., & Dabla, P. K. (2015). Oxidative stress and antioxidants in the hypertension-a current review. Current Hypertension Reviews, 11(2), 132-142. https://* doi.org/10.2174/1573402111666150529130922.
12. Tan, B. L., Norhaizan, M. E., & Liew, W. P. (2018). Nutrients and Oxidative Stress: Friend or Foe? Oxidative Medicine and Cellular Longevity, 9719584, 1-24. https:// doi.org/10.1155/2018/9719584.
13. Radad, K., Al-Shraim, M., Al-Emam, A., Wang, F., Kranner, B., Rausch, W. D., & Moldzio, R. (2019). Rotenone: from modeling to implication in Parkinson's disease. Folia Neuropathologica, 57(4), 317–326. https://doi.org/10.5114/fn.2019.89857
14. Bisbal, M., & Sanchez, M. (2019). Neurotoxicity of the pesticide rotenone on neuronal polarization: a mechanistic approach. Neural Regeneration Research. 14(5), 762- 766. https://doi.org/10.4103/1673-5374.249847.
15. Jayaraj, R. L., Beiram, R., Azimullah, S., Meeran M. F. N., Ojha, S. K., Âdem, A., & Jalal, F. Y. (2021). Noscapine prevents rotenone-induced in neurotoxicity: Involvement of oxidative stress, neuroinflammation and autophagy pathways. Molecules, 26(15), 4627. https:// doi.org/10.3390/molecules26154627.
16. Clarke, W. B., Webber, C. E., & Koekebakker, M. (1987). Lithium and boron in human blood. Journal of Laboratory and Clinical Medicine, 109(2), 155-158.
17. Jones, J. G., (2016). Hepatic glucose and lipid metabolism. Diabetologia, 59, 1098-1103. https://doi.org/10.1007/s00125-016-3940-5.
18. Penland, J. G., (1998). The importance of boron nutrition for brain and psychological function. Biological Trace Element Research, 66, 299-317. https://doi.org/10.1007/ BF02783144.
19. Hegsted, M., Keenan, M. J., Siver, F., & Wozniak, P., (1991). Effect of boron on vitamin D deficient rats. Biological Trace Element Research, 28, 243-255. https://doi.org/10.1007/BF02990471.
20. Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological Trace Element Research, 186, 31-51. https://doi.org/10.1007/ s12011-018-1284-3.
21. Ince, S., Kucukkurt, I., Cigerci, I. H., Fidan, A. F., & Eryavuz, A., (2010). The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. Journal of Trace Elements in Medicine and Biology, 24(3), 161-164.https://doi.org/10.1016/j.jtemb.2010.01.003.
22. Nielsen, F. H. (2014). Update on human health effects of boron. Journal of Trace Elements in Medicine and Biology, 28, 383-387. https://doi.org/10.1016/j. jtemb.2014.06.023.
23. Ghaffari, F., Moghaddam, A. H., & Zare, M., (2018). Neuroprotective effect of quercetin nanocrystal in a 6-Hydroxydopamine model of parkinson disease: Biochemical and behavioral evidence. Basic Clinical Neuroscience, 9(5), 317-324. https://doi.org/10.32598/ bcn.9.5.317.
24. El-Horany, H. E., Abd El-latif, R. N., ElBatsh, M. M., & Emam M. N., (2016). Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of parkinson's disease: modulating autophagy (quercetin on experimental parkinson's disease). Journal of Biochemical and Molecular Toxicology, 30(7),360-369. https://doi.org/10.1002/jbt.21821.
25. Karuppagounder, S. S., Madathil, S. K., Pandey, M., Haobam, R., Rajamma, U., & Mohanakumar K. P., (2013). Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of parkinson's disease in rats. Neuroscience, 236, 136-148. https://doi.org/10.1016/j. neuroscience. 2013.01.032.
26. Bors, W., Heller, W., Michel, C., & Saran, M. (1990). Flavonoid as antioxidants: Determination of radicalscavenging efficiencie. Methods in Enzymology, 186, 334-355. https://doi.org/10.1016/0076-6879(90)86128-i.
27. Sharma, S., Raj, K., & Singh, S., (2020). Neuroprotective effect of quercetin in combination with piperine against rotenone- and iron supplement–induced parkinson’s disease in experimental rats. Neurotoxicity Research, 37,198-209. https://doi.org/10.1007/s12640-019-00120-z.
28. Ay, M., Luo, J., Langley, M., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G., (2017). Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and mitopark transgenic mouse models of parkinson’s disease. Journal of Neurochemistry, 141(5), 766-782. https://doi.org/10.1111/jnc.14033.
29. Shen, P., Lin, W., Deng, X., Ba, X., Han, L., Chen, Z., ... & Tu, S. (2021). Potential implications of quercetin in autoimmune diseases. Frontiers in Immunology, 12, 689044. https://doi.org/10.3389/fimmu.2021.689044.
30. Beutler, E., Duron, O., Kelly, & B.M. (1963). Improved method for the determination of blood glutathione. Journal of Laboratory and Clinical Medicine, 61, 882-888. PMID: 13967893.
31. Tekin, M., Kaya-Yertutanol, F. D., Çevreli, B., Özdoğru, A. A., Kulaksız, H., & Uzbay, İ. T. (2021). Sodium valproate improves sensorimotor gating deficit induced by sleep deprivation at low doses. Turkish Journal of Medical Sciences, 51(3), 1521-1530. Doi: 10.3906/sag-2011-229. https://doi.org/10.3906/sag-2011-229.
32. Kujawska, M., & Jodynis-Liebert, J., (2018). Polyphenols in parkinson’s disease: A systematic review of in vivo studies. Nutrients, 10(5), 642. https://doi.org/10.3390/nu10050642.
33. Lueptow, L. M. (2017). Novel object recognition test for the investigation of learning and memory in mice. Journal of Visualized Experiments: JoVE, (126), 55718. https://doi.org/10.3791/55718.
34. Fernandes, V. S., Santos, J. R., Leão, A. H., Medeiros, A. M., Melo, T. G., Izídio, G. S., … & Silva, R. H. (2012). Repeated treatment with a low dose of reserpine as a progressive model of Parkinson's disease. Behavioural Brain Research, 231(1), 154-163. https://doi.org/10.1016/j.bbr.2012.03.008.
35. Ayhanci, A., Tanriverdi, D. T., Sahinturk, V., Cengiz, M., Appak-Baskoy, S., & Sahin, I. K. (2020). Protective effects of boron on cyclophosphamide-induced bladder damage and oxidative stress in rats. Biological Trace Element Research, 197, 184-191. https://doi.org/10.1007/s12011-019-01969-z.
36. Kar, F., Hacioglu, C., Senturk, H., Donmez, D. B., & Kanbak, G. (2020). The role of oxidative stress, renal inflammation, and apoptosis in post ischemic reperfusion injury of kidney tissue: The protective effect of dose-dependent boric acid administration. Biological Trace Element Research, 195, 150-158. https://doi. org/10.1007/s12011-019-01824-1.
37. Nicholas, V. C., & Hunt, R. C. D., (2020). Diadenosine phosphates and S-adenosylmethionine: Novel boron binding biomolecules detected by capillary electrophoresis. Neurotoxicity Research, 37, 198-209. https://doi.org/10.1016/s0304-4165(01)00130-1.
38. Sogut, I., Oglakcı, A., Kartkaya, K., Kusat Ol K., Sogut, M. S., Kanbak, G., & Inal, M. E. (2015). Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Experimental and Therapeutic Medicine, 9, 1023-1027. https://doi.org/10.3892/etm.2014.2164.
39. Romuk, E. B., Szczurek, W., Nowak, P. G., Hudziec, E., Chwalińska, E., & Birkner, E. (2016). Effects of propofol on the liver oxidative-antioxidant balance in a rat model of parkinson's disease. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, 25(5), 815-820. https://doi.org/10.17219/acem/36459.
40. [40] Boyina, H. K., Geethakhrishnan, S. L., Panuganti, S., Gangarapu, K., Devarakonda, K. P., Bakshi, V., & Guggilla, S. R. (2020). In silico and in vitro studies on quercetin as potential anti-parkinson agent. Advances in Experimental Biology, 1195, 1-11. https://doi. org/10.1007/978-3-030-32633-3_1.
41. Deny Joseph, K. M., & Muralidhara. (2015). Combined oral supplementation of fish oil and quercetin enhances neuroprotection in a chronic rotenone rat model: relevance to parkinson’s disease. Neurochemical Research, 40(5), 894-905. https://doi.org/10.1007/s11064-015-1542-0