TY  - JOUR
T1  - The role of oxidative stress in the protective effect of boric acid against glutamate excitotoxicity in C6 glioma cells
TT  - Borik asidin C6 glioma hücrelerinde glutamat eksitotoksisitesine karşı koruyucu etkinliğinde oksidatif stresin rolü
AU  - Öztürk, Ayşegül
AU  - Taşkıran, Ahmet Şevki
AU  - Gündoğdu, Emin
PY  - 2025
DA  - April
Y2  - 2025
DO  - 10.30728/boron.1519354
JF  - Journal of Boron
PB  - TENMAK Bor Araştırma Enstitüsü
WT  - DergiPark
SN  - 2149-9020
SP  - 1
EP  - 9
VL  - 10
IS  - 1
LA  - en
AB  - This study designed to investigate the biochemical changes in glial cells' oxidant/antioxidant systems in response to glutamate-induced excitotoxicity of boric acid (BA). The present study employed C6 glial cells. For the study, cells were separated into 4 groups as control, glutamate (10mM), glutamate+BA (0,23; 0,46; 0,93; 1,87 and 3,75 μg/mL), and BA (0,23; 0,46; 0,93; 1,87 and 3,75 μg/mL). The control group was not treated. The cells in the glutamate group were treated with 10 mM glutamate for 24 hours. BA was administered one hour prior to the addition of glutamate and incubated for 24 hours. The viability of the cells was evaluated using an XTT assay. Commercial kits were used for biochemical analyses. Significance was set at less than 0.05. The biochemical analysis revealed that the levels of malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide snythase (iNOS), neuronal nitric oxide synthase (nNOS), and total oxidant status (TOS) were elevated in the glutamate group compared to the control group (p
KW  - Boric Acid
KW  - C6 Cells
KW  - Glutamate Excitotoxicity
KW  - Oxidative Stress
N2  - Bu çalışma, borik asidin (BA) glutamat ile indüklenen eksitotoksisiteye karşı glial hücrelerde meydana gelen oksidan/antioksidan sistem değişikliklerini biyokimyasal olarak incelemek amacıyla tasarlanmıştır. Bu çalışmada C6 glial hücreleri kullanılmıştır. Hücreler kontrol, glutamat (10mM), glutamat+BA(0,23; 0,46; 0,93; 1,87 ve 3,75 μg/mL) ve BA (0,23; 0,46; 0,93; 1,87 ve 3,75 μg/ml) olmak üzere 4 gruba ayrılmıştır. Kontrol grubuna herhangi bir tedavi yapılmamıştır. Glutamat grubundaki hücreler 24 saat boyunca 10 mM glutamat ile muamele edilmiştir. BA ise glutamat eklenmeden 1 saat önce verildi ve 24 saat boyunca inkübe edilmiştir. Hücre canlılığı XTT testi ile ölçülmüştür. Biyokimyasal analizler için ticari kitler kullanılmıştır. Anlamlılık 0.05’ten küçük olarak kabul edilmiştir. Biyokimyasal analiz ile glutamat grubunda malondialdehit (MDA), nitrik oksit (NO), indüklenmiş nitrik oksit sentaz (iNOS), nöronal nitrik oksit sentaz (nNOS) ve toplam oksidant (TOS) seviyelerinin kontrol grubuna göre arttığı (p
CR  - [1] Wang, Y., & Qin, Z. (2010). Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis, 15(11), 1382-1402. https://doi.org/10.1007/s10495-010-0481-0
CR  - [2] Daniele, S. G., Trummer, G., Hossmann, K. A., Vrselja, Z., Benk, C., Gobeske, K. T., … & Sestan, N. (2021). Brain vulnerability and viability after ischaemia. Nature Reviews Neuroscience, 22(9), 553-572. https://doi.org/10.1038/s41583-021-00488-y
CR  - [3] Dong, X., Wang, Y., & Qin, Z. (2009). Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica, 30(4), 379-387. https://doi.org/10.1038/aps.2009.24
CR  - [4] Kritis, A. A., Stamoula, E. G., Paniskaki, K. A., & Vavilis, T. D. (2015). Researching glutamate-induced cytotoxicity in different cell lines: A comparative/collective analysis/study. Frontiers in Cellular Neuroscience, 9. https://doi.org/10.3389/fncel.2015.00091
CR  - [5] Felek, H., Çatal, T., Yulak, F., Filiz, A. K., & Karabulut, S. (2024). The effect of myostatin on glutamate excitotoxicity induced in SH-SY5Y cell line. Health Sciences Student Journal, 4(1), 1-6. Erişim Adresi: https://ojs.healthssj.com/index.php/panel/article/view/15
CR  - [6] Barbeito, L. H., Pehar, M., Cassina, P., Vargas, M. R., Peluffo, H., Viera, L., … & Beckman, J. S. (2004). A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Research Reviews, 47(1-3), 263-274. https://doi.org/10.1016/j.brainresrev.2004.05.003
CR  - [7] Hertz, L. (2006). Glutamate, a neurotransmitter-and so much more. Neurochemistry International, 48(6-7), 416-425. https://doi.org/10.1016/j.neuint.2005.12.021
CR  - [8] Pope, S. A., Milton, R., & Heales, S. J. (2008). Astrocytes protect against copper-catalysed loss of extracellular glutathione. Neurochemical Research, 33(7), 1410-1418. https://doi.org/10.1007/s11064-008-9602-3
CR  - [9] Quincozes-Santos, A., & Gottfried, C. (2011). Resveratrol modulates astroglial functions: Neuroprotective hypothesis. Annals of the New York Academy of Sciences, 1215(1), 72-78. https://doi.org/10.1111/j.1749-6632.2010.05857.x
CR  - [10] Benda, P., Lightbody, J., Sato, G., Levine, L., & Sweet, W. (1968). Differentiated rat glial cell strain in tissue culture. Science, 161(3839), 370-371. https://doi.org/10.1126/science.161.3839.370
CR  - [11] Gutteridge, J. M. C., & Halliwell, B. (2010). Antioxidants: Molecules, medicines, and myths. Biochemical and Biophysical Research Communications, 393(4), 561-564. https://doi.org/10.1016/j.bbrc.2010.02.071
CR  - [12] Karademir M., Öztürk, A., Yulak, F., Özkaraca, M., & Taskiran, A. S. (2024). Unveiling the protective potential of sugammadex against ptz-induced epileptic seizures in mice: A comprehensive study on oxidative stress, apoptosis, and autophagy. Neurochemical Journal, 18(2), 338-347. https://doi.org/10.1134/s1819712424020181
CR  - [13] Azimullah, S., Meeran, M. F., Ayoob, K., Arunachalam, S., Ojha, S., & Beiram, R. (2023). Tannic acid mitigates rotenone-induced dopaminergic neurodegeneration by inhibiting inflammation, oxidative stress, apoptosis, and glutamate toxicity in rats. International Journal of Molecular Sciences, 24(12), 9876. https://doi.org/10.3390/ijms24129876
CR  - [14] Brocardo, P. S., Gil-Mohapel, J., & Christie, B. R. (2011). The role of oxidative stress in fetal alcohol spectrum disorders. Brain Research Reviews, 67(1-2), 209-225. https://doi.org/10.1016/j.brainresrev.2011.02.001
CR  - [15] Javed, H., Azimullah, S., Haque, M. E., & Ojha, S. K. (2016). Cannabinoid type 2 (CB2) receptors activation protects against oxidative stress and neuroinflammation associated dopaminergic neurodegeneration in rotenone model of parkinson’s disease. Frontiers in Neuroscience, 10. https://doi.org/10.3389/fnins.2016.00321
CR  - [16] Ergül, M., & Taşkıran, A. Ş. (2021). Thiamine protects glioblastoma cells against glutamate toxicity by suppressing oxidative/endoplasmic reticulum stress. Chemical and Pharmaceutical Bulletin, 69(9), 832-839. https://doi.org/10.1248/cpb.c21-00169
CR  - [17] Salim, S. (2017). Oxidative stress and the central nervous system. The Journal of Pharmacology and Experimental Therapeutics, 360(1), 201-205. https://doi.org/10.1124/jpet.116.237503
CR  - [18] Nielsen, F. H. (2008). Is boron nutritionally relevant? Nutrition Reviews, 66(4), 183-191. https://doi.org/10.1111/j.1753-4887.2008.00023.x
CR  - [19] Qiu, L., Zhu, C.-L., Wang, X.-Y., & Xu, F.-L. (2007). Changes of cell proliferation and differentiation in the developing brain of mouse. Neuroscience Bulletin, 23(1), 46-52. https://doi.org/10.1007/s12264-007-0007-0
CR  - [20] Barrón-González, M., Montes-Aparicio, A. V., Cuevas-Galindo, M. E., Orozco-Suárez, S., Barrientos, R., Alatorre, A., … & Soriano-Ursúa, M. A. (2023). Boroncontaining compounds on neurons: Actions and potential applications for treating neurodegenerative diseases. Journal of Inorganic Biochemistry, 238, 112027. https://doi.org/10.1016/j.jinorgbio.2022.112027
CR  - [21] Barranco, W. T., & Eckhert, C. D. (2006). Cellular changes in boric acid-treated DU-145 prostate cancer cells. British Journal of Cancer, 94(6), 884-890. https://doi.org/10.1038/sj.bjc.6603009
CR  - [22] Sogut, I., Oglakcı, A., Kartkaya, K., Ol, K. K., Sogut, M. S., Kanbak, G., & Inal, M. E. (2014). Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Experimental and Therapeutic Medicine, 9(3), 1023-1027. https://doi.org/10.3892/etm.2014.2164
CR  - [23] Ince, S., Kucukkurt, I., Cigerci, I. H., Fatih Fidan, A., & 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
CR  - [24] Yousefzadehmoghaddam, R., Hassanpour, M., Öztürk, A., & Karabulut, S., (2023). Investigation of the effect of galium aparine extract on glutamate excitotoxicity induced in C6-glioma cell line. Health Sciences Student Journal, 3(1), 8-18. Retrieved from https://journals.indexcopernicus.com/api/file/viewByFileId/1773565
CR  - [25] Taskiran, A. S., & Ergul, M. (2021). The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play. Metabolic Brain Disease, 36(7), 1985-1993. https://doi.org/10.1007/s11011-021-00793-6
CR  - [26] Dirik, H., & Joha, Z. (2023). Investigation of the effect of sugammadex on glutamate-induced neurotoxicity in C6 cell line and the roles played by nitric oxide and oxidative stress pathways. Fundam Clin Pharmacol, 37(4), 786-793. https://doi.org/10.1111/fcp.12890
CR  - [27] Gömeç, M., İpek, G., Öztürk, A., & Şahin İnan, D. (2022). Effect of wheat germ oil on wound healing: An in vitro study in fibroblast cells. Turkish Journal of Science and Health, 3(3), 230-235. https://doi.org/10.51972/tfsd.1128533
CR  - [28] Erel, O. (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical Biochemistry, 37(2), 112-119. https://doi.org/10.1016/j.clinbiochem.2003.10.014
CR  - [29] Taşkıran, A. Ş., & Topçu, A. (2023). Investigation of the protective role of quercetin on oxidative stress and endoplasmic stress pathway in 4-aminopyridine-induced neuronal damage. Turkish Journal of Agriculture - Food Science and Technology, 11(1), 2505-2511. https://doi.org/10.24925/turjaf.v11is1.2505-2511.6413
CR  - [30] Filiz, A. K., Joha, Z., & Yulak, F. (2021). Mechanism of anti-cancer effect of β-glucan on SH-sy5y cell line. Bangladesh Journal of Pharmacology, 16(4), 122-128. https://doi.org/10.3329/bjp.v16i4.54872
CR  - [31] Gavande, N., Kim, H.-L., Doddareddy, M. R., Johnston, G. A., Chebib, M., & Hanrahan, J. R. (2013). Design, synthesis, and pharmacological evaluation of fluorescent and biotinylated antagonists of ρ1 GABAC Receptors. ACS Medicinal Chemistry Letters, 4(4), 402-407. https://doi.org/10.1021/ml300476v
CR  - [32] Soriano-Ursúa, M. A., Bello, M., Hernández-Martínez, C. F., Santillán-Torres, I., Guerrero-Ramírez, R., Correa-Basurto, J., … & Trujillo-Ferrara, J. G. (2018). Cell-based assays and molecular dynamics analysis of a boron-containing agonist with different profiles of binding to human and guinea pig beta2 adrenoceptors. European Biophysics Journal, 48(1), 83-97. https://doi. org/10.1007/s00249-018-1336-9
CR  - [33] Vernekar, S. K., Hallaq, H. Y., Clarkson, G., Thompson, A. J., Silvestri, L., Lummis, S. C., & Lochner, M. (2010). Toward biophysical probes for the 5-HT3 receptor: Structure−activity relationship study of granisetron derivatives. Journal of Medicinal Chemistry, 53(5), 2324-2328. https://doi.org/10.1021/jm901827x
CR  - [34] Çolak, S., Geyikoğlu, F., Keles, O. N., Türkez, H., Topal, A., & Unal, B. (2011). The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicology and Industrial Health, 27(8), 700-710. https://doi.org/10.1177/0748233710395349
CR  - [35] Kar, F., Hacioğlu, C., & Kaçar, S. (2022). The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways. Environmental Toxicology, 38(1), 70-77. https://doi.org/10.1002/tox.23662
CR  - [36] Kizilay, Z., Erken, H., Çetin, N., Aktaş, S., Abas, B., & Yılmaz, A. (2016). Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury. Neural Regeneration Research, 11(10), 1660. https://doi.org/10.4103/1673-5374.193247
CR  - [37] Zafar, H., & Ali, S. (2013). Boron inhibits the proliferating cell nuclear antigen index, molybdenum containing proteins and ameliorates oxidative stress in hepatocellular carcinoma. Archives of Biochemistry and Biophysics, 529(2), 66-74. https://doi.org/10.1016/j.abb.2012.11.008
CR  - [38] Ince, S., Kucukkurt, I., Demirel, H. H., Acaroz, D. A., Akbel, E., & Cigerci, I. H. (2014). Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108, 197-204. https://doi.org/10.1016/j.chemosphere.2014.01.038
CR  - [39] Ayhanci, A., Tanriverdi, D. T., Sahinturk, V., Cengiz, M., Appak-Baskoy, S., & Sahin, I. K. (2019). Protective effects of boron on cyclophosphamide-induced bladder damage and oxidative stress in rats. Biological Trace Element Research, 197(1), 184-191. https://doi.org/10.1007/s12011-019-01969-z
CR  - [40] Coban, F. K., Ince, S., Kucukkurt, I., Demirel, H. H., & Hazman, O. (2014). Boron attenuates malathioninduced oxidative stress and acetylcholinesterase inhibition in rats. Drug and Chemical Toxicology, 38(4), 391-399. https://doi.org/10.3109/01480545.2014.974109
CR  - [41] Acaroz, U., Ince, S., Arslan-Acaroz, D., Gurler, Z., Kucukkurt, I., Demirel, H. H., … & Zhu, K. (2018). The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food and Chemical Toxicology, 118, 745-752. https://doi.org/10.1016/j.fct.2018.06.029
CR  - [42] Ataizi, Z. S., Ozkoc, M., Kanbak, G., Karimkhani, H., Burukoglu Donmez, D., Ustunisik, N., & Ozturk, B. (2019). Evaluation of the neuroprotective role of boric acid in preventing traumatic brain injury-mediated oxidative stress. Turkish Neurosurgery, 31(4). https://doi.org/10.5137/1019-5149.jtn.25692-18.4
CR  - [43] Yavuz, E., Çevik, G., Çevreli, B., & Serdaroğlu Kaşıkçı, E. (2023). Effect of boric acid and quercetin combination on oxidative stress/ cognitive function in parkinson model. Journal of Boron, 8(3), 85-91. https://doi.org/10.30728/boron.1215949
CR  - [44] Filiz, A. K., Öztürk, A. (2021). The effect of carbamazepine against glutamate-induced cytotoxicity in the C6 cell line. International Journal of Scientific and Technological Research, 7(8). https://doi.org/10.7176/jstr/7-08-09
CR  - [45] Yıldızhan, K., & Öztürk, A. (2022). Quipazine treatment exacerbates oxidative stress in glutamate-induced HT-22 neuronal cells. The European Research Journal, 8(4), 521-528. https://doi.org/10.18621/eurj.1027423
CR  - [46] Çakır Çanak, T., Akpınar, S., & Serhatlı, E. (2017). Homopolymerization and synthesis of a new methacrylate monomer bearing a boron side group: Characterization and determination of monomer reactivity ratios with styrene. Turkish Journal of Chemistry, 41, 209-220. https://doi.org/10.3906/kim-1603-106
CR  - [47] Şahin, B., & Karabulut, S. (2022). Sugammadex causes C6 glial cell death and exacerbates hydrogen peroxideinduced oxidative stress. Cumhuriyet Medical Journal, 44(1), 22-27. https://doi.org/10.7197/cmj.1069629
CR  - [48] Dohi, K., Satoh, K., Nakamachi, T., Yofu, S., Hiratsuka, K., Nakamura, S., … & Aruga, T. (2007). Does Edaravone (MCI-186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury? Antioxidants & Redox Signaling, 9(2), 281-287. https://doi.org/10.1089/ars.2007.9.281
CR  - [49] Topal Canbaz, G., Keskin, Z. S., Yokuş, A., & Aslan, R. (2023). Biofabrication of copper oxide nanoparticles using solanum tuberosum L. var. Vitelotte: Characterization, antioxidant and antimicrobial activity. Chemical Papers, 77(8), 4277-4284. https://doi.org/10.1007/s11696-023-02776-6
CR  - [50] Sahin, N., Akdemir, F., Orhan, C., Aslan, A., Agca, C. A., Gencoglu, H., … & Sahin, K. (2012). A novel nutritional supplement containing chromium picolinate, phosphatidylserine, docosahexaenoic acid, and boron activates the antioxidant pathway Nrf2/HO-1 and protects the brain against oxidative stress in high-fat-fed rats. Nutritional Neuroscience, 15(5), 42-47. https://doi.org/10.1179/1476830512y.0000000018
CR  - [51] Hazman, Ö., Bozkurt, M. F., Fidan, A. F., Uysal, F. E., & Çelik, S. (2018). The effect of boric acid and borax on oxidative stress, inflammation, er stress and apoptosis in cisplatin toxication and nephrotoxicity developing as a result of toxication. Inflammation, 41(3), 1032-1048. https://doi.org/10.1007/s10753-018-0756-0
CR  - [52] Hacioglu, C., Kar, F., Kar, E., Kara, Y., & Kanbak, G. (2020). Effects of curcumin and boric acid against neurodegenerative damage induced by amyloid beta (1-42). Biological Trace Element Research. 199, 3793-3800. https://doi.org/10.1007/s12011-020-02511-2
UR  - https://doi.org/10.30728/boron.1519354
L1  - https://dergipark.org.tr/en/download/article-file/4084202
ER  -