Öz
Aim: Neurodegeneration is the progressive loss and structural deterioration of neuronal cells. Hydrogen peroxide (H2O2) is formed by dismutation and causes oxidative stress in neuronal cells. Venlafaxine is a drug that increases both serotonin and noradrenaline in the synaptic gap.In this study, the effect of venlafaxine on H2O2-induced cytotoxicity in C6 cells was investigated.
Methods: First of all, different doses of venlafaxine (25, 50, and 100 µM) were tried to find the appropriate dose in C6 glioma cells. Then, the effect of venlafaxine on H2O2-induced cytotoxicity in the cells was investigated. For this purpose, cell viability rate, proinflammatory markers IL-1β and TNF-α, and NO and iNOS levels were examined by ELISA kits.
Results: H2O2-treated caused cytotoxicity in the C6 glioma cells; when venlafaxine 25, 50, and 100 μM doses were evaluated in terms of cell viability, it was observed that the 100 μM venlafaxine applied group significantly increased cell viability compared to the other groups. When we look at the levels of IL-1β and TNF-α, it is observed that there is an increase in the H2O2 applied group and a significant decrease in the venlafaxine (100 μM) applied group. It was observed that NO and iNOS levels increased in the H2O2 applied group compared to the other groups. It was observed that Venlafaxine treatment reduced the increased NO and iNOS levels caused by H2O2.
Conclusion: The study results showed that venlafaxine may have a protective effect on H2O2-induced cytotoxicity in C6 glioma cells.
Anahtar Kelimeler
Kaynakça
- 1. Kim GH, Kim JE, Rhie SJ, Yoon S The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol. 2015;24(4):325-40. doi: 10.5607/en.2015.24.4.325.
- 2. Lin MT, Beal MF Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787-95. doi: 10.1038/nature05292.
- 3. Coutens B, Yrondi A, Rampon C, Guiard BP Psychopharmacological properties and therapeutic profile of the antidepressant venlafaxine. Psychopharmacology (Berl). 2022 Sep;239(9):2735-52. doi: 10.1007/s00213-022-06203-8.
- 4. Laux G, Klimke A. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran. NeuroPsychopharmacotherapy. 2022;1-27. doi: 10.1007/978-3-319-56015-1_414-1
- 5. Wang S-M, Han C, Bahk W-M, Lee S-J, Patkar AA, Masand PS, Pae C-U Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam Med J. 2018;54(2):101-12. doi: 10.4068/cmj.2018.54.2.101.
- 6. Mahesh R, Kim S-J The protective effects of insulin on hydrogen peroxide-induced oxidative stress in C6 glial cells. Biomolecules & Therapeutics. 2009;17(4):395-402. doi: 10.4062/biomolther.2009.17.4.395.
- 7. Chidawanyika T, Supattapone S Hydrogen Peroxide-induced Cell Death in Mammalian Cells. J Cell Signal. 2021;2(3):206-11. doi: 10.33696/signaling.2.052.
- 8. Doğan M, Yıldızhan K Investigation of the effect of paracetamol against glutamate-induced cytotoxicity in C6 glia cells. Cumhuriyet Science Journal. 2021;42:789-94. doi: 10.17776/csj.999199.
- 9. Şahin B, KARABULUT S Sugammadex Causes C6 Glial Cell Death and Exacerbates Hydrogen Peroxide-Induced Oxidative Stress. Cumhuriyet Medical Journal. 2022;44:22-7. doi: 10.7197/cmj.1069629.
- 10. Taskiran AS, Ergul M Oxytocin promotes C6 glial cell death and aggravates hydrogen peroxide-induced oxidative stress. INNOSC Theranostics and Pharmacological Sciences. 2020;3(1):939. doi: 10.36922/itps.v3i1.939.
- 11. Yu J, Roh S, Lee J-S, Yang B-H, Choi MR, Chai YG, Kim SH The effects of venlafaxine and dexamethasone on the expression of HSP70 in rat C6 glioma cells. Psychiatry Investig. 2010;7(1):43-8. doi: 10.4306/pi.2010.7.1.43.
- 12. Yıldızhan K, Huyut Z, Altındağ F, Ahlatcı A Effect of selenium against doxorubicin-induced oxidative stress, inflammation, and apoptosis in the brain of rats: Role of TRPM2 channel. Indian Journal of Biochemistry and Biophysics (IJBB). 2023;60:177-85. doi:10.56042/ijbb.v60i3.67941
- 13. Niedzielska E, Smaga I, Gawlik M, Moniczewski A, Stankowicz P, Pera J, Filip M Oxidative stress in neurodegenerative diseases. Mol Neurobiol. 2016;53(6):4094-4125. doi: 10.1007/s12035-015-9337-5.
- 14. Wang H, Zhou X, Huang J, Mu N, Guo Z, Wen Q, Wang R, Chen S, Feng Z-P, Zheng W The role of Akt/FoxO3a in the protective effect of venlafaxine against corticosterone-induced cell death in PC12 cells. Psychopharmacology (Berl). 2013;228(1):129-41. doi: 10.1007/s00213-013-3017-9.
- 15. Eren I, Nazıroğlu M, Demirdaş A, Çelik Ö, Uğuz AC, Altunbaşak A, Özmen İ, Uz E Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochemi Res. 2007;32(3):497-505. doi: 10.1007/s11064-006-9258-9.
- 16. Lister INE, Ginting CN, Girsang E, Nataya ED, Azizah AM, Widowati W Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory, antinecrotic, antioxidant potency. Saudi Pharm J. 2020;28(10):1182-9. doi: 10.1016/j.jsps.2020.08.007.
- 17. Abdel-Wahab BA, Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav. 2011;100(1):59-65. doi: 10.1016/j.pbb.2011.07.015.
- 18. Yazğan Y, Yazğan B Gossypin Regulated Doxorubicin-Induced Oxidative Stress and Inflammation in H9c2 Cardiomyocyte Cells. Medical Records. 2024;6(1):44-9. doi:10.37990/medr.1383719.
- 19. Turner MD, Nedjai B, Hurst T, Pennington DJ Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563-2582. doi: 10.1016/j.bbamcr.2014.05.014.
- 20. Fraczek M, Kurpisz M Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa. J Androl. 2007;28(2):325-33. doi: 10.2164/jandrol.106.001149.
- 21. Yıldızhan K, Nazıroğlu M Glutathione depletion and parkinsonian neurotoxin MPP+-induced TRPM2 channel activation play central roles in oxidative cytotoxicity and inflammation in microglia. Mol Neurobiol. 2020;57(8):3508-25. doi: 10.1007/s12035-020-01974-7.
- 22. Korhonen R, Lahti A, Kankaanranta H, Moilanen E Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(4):471-9. doi: 10.2174/1568010054526359.
- 23. Aktan F iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639-53. doi: 10.1016/j.lfs.2003.10.042.
- 24. Quincozes-Santos A, Bobermin LD, Latini A, Wajner M, Souza DO, Gonçalves C-A, Gottfried C Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PloS One. 2013;8(5):e64372. doi: 10.1371/journal.pone.0064372.
- 25. Giasson BI, Ischiropoulos H, Lee VM-Y, Trojanowski JQ The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer’s and Parkinson’s diseases. Free Radic Biol Med. 2002;32(12):1264-75. doi: 10.1016/s0891-5849(02)00804-3.
Öz
Amaç: Nörodejenerasyon, nöron hücrelerinin ilerleyici kaybı ve yapısal bozulmasıdır. Hidrojen peroksit (H2O2) dismutasyonla oluşur ve nöron hücrelerinde oksidatif strese neden olur. Venlafaksin, sinaptik boşlukta hem serotonini hem de noradrenalini artıran bir ilaçtır.Bu çalışmada venlafaksi’nin C6 hücrelerinde H2O2 kaynaklı sitotoksisite üzerindeki etkisini araştırıldı.
Yöntem: Öncelikle C6 glioma hücrelerinde uygun dozu bulmak için farklı dozlarda venlafaksin (25, 50 ve 100 µM) denendi. Daha sonra venlafaksi’nin hücrelerde H2O2 kaynaklı sitotoksisite üzerine etkisi araştırıldı. Bu amaçla hücre canlılık oranı, IL-1β, TNF-α, NO ve iNOS düzeyleri ELISA kitleri ile incelendi.
Bulgular: H2O2 ile inkübasyon C6 glioma hücrelerinde sitotoksisiteye neden oldu. Venlafaksin 25, 50 ve 100 μM dozları hücre canlılığı açısından değerlendirildiğinde, 100 μM venlafaksin uygulanan grubun diğer gruplara göre hücre canlılığını anlamlı düzeyde arttırdığı görüldü. IL-1β ve TNF-α düzeylerine bakıldığında H2O2 uygulanan grupta artış, venlafaksin (100 μM) uygulanan grupta ise IL-1β ve TNF-α düzeylerinde anlamlı oranda azalma olduğu görüldü. H2O2 uygulanan grupta NO ve iNOS düzeylerinin diğer gruplara göre arttığı gözlendi. Venlafaksin tedavisinin H2O2'nin neden olduğu artan NO ve iNOS düzeylerini azalttığı görüldü.
Sonuç: Çalışma sonuçları venlafaksinin C6 glioma hücrelerinde H2O2 kaynaklı sitotoksisite üzerinde koruyucu etkiye sahip olabileceğini gösterdi.
Anahtar Kelimeler
Kaynakça
- 1. Kim GH, Kim JE, Rhie SJ, Yoon S The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol. 2015;24(4):325-40. doi: 10.5607/en.2015.24.4.325.
- 2. Lin MT, Beal MF Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787-95. doi: 10.1038/nature05292.
- 3. Coutens B, Yrondi A, Rampon C, Guiard BP Psychopharmacological properties and therapeutic profile of the antidepressant venlafaxine. Psychopharmacology (Berl). 2022 Sep;239(9):2735-52. doi: 10.1007/s00213-022-06203-8.
- 4. Laux G, Klimke A. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran. NeuroPsychopharmacotherapy. 2022;1-27. doi: 10.1007/978-3-319-56015-1_414-1
- 5. Wang S-M, Han C, Bahk W-M, Lee S-J, Patkar AA, Masand PS, Pae C-U Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam Med J. 2018;54(2):101-12. doi: 10.4068/cmj.2018.54.2.101.
- 6. Mahesh R, Kim S-J The protective effects of insulin on hydrogen peroxide-induced oxidative stress in C6 glial cells. Biomolecules & Therapeutics. 2009;17(4):395-402. doi: 10.4062/biomolther.2009.17.4.395.
- 7. Chidawanyika T, Supattapone S Hydrogen Peroxide-induced Cell Death in Mammalian Cells. J Cell Signal. 2021;2(3):206-11. doi: 10.33696/signaling.2.052.
- 8. Doğan M, Yıldızhan K Investigation of the effect of paracetamol against glutamate-induced cytotoxicity in C6 glia cells. Cumhuriyet Science Journal. 2021;42:789-94. doi: 10.17776/csj.999199.
- 9. Şahin B, KARABULUT S Sugammadex Causes C6 Glial Cell Death and Exacerbates Hydrogen Peroxide-Induced Oxidative Stress. Cumhuriyet Medical Journal. 2022;44:22-7. doi: 10.7197/cmj.1069629.
- 10. Taskiran AS, Ergul M Oxytocin promotes C6 glial cell death and aggravates hydrogen peroxide-induced oxidative stress. INNOSC Theranostics and Pharmacological Sciences. 2020;3(1):939. doi: 10.36922/itps.v3i1.939.
- 11. Yu J, Roh S, Lee J-S, Yang B-H, Choi MR, Chai YG, Kim SH The effects of venlafaxine and dexamethasone on the expression of HSP70 in rat C6 glioma cells. Psychiatry Investig. 2010;7(1):43-8. doi: 10.4306/pi.2010.7.1.43.
- 12. Yıldızhan K, Huyut Z, Altındağ F, Ahlatcı A Effect of selenium against doxorubicin-induced oxidative stress, inflammation, and apoptosis in the brain of rats: Role of TRPM2 channel. Indian Journal of Biochemistry and Biophysics (IJBB). 2023;60:177-85. doi:10.56042/ijbb.v60i3.67941
- 13. Niedzielska E, Smaga I, Gawlik M, Moniczewski A, Stankowicz P, Pera J, Filip M Oxidative stress in neurodegenerative diseases. Mol Neurobiol. 2016;53(6):4094-4125. doi: 10.1007/s12035-015-9337-5.
- 14. Wang H, Zhou X, Huang J, Mu N, Guo Z, Wen Q, Wang R, Chen S, Feng Z-P, Zheng W The role of Akt/FoxO3a in the protective effect of venlafaxine against corticosterone-induced cell death in PC12 cells. Psychopharmacology (Berl). 2013;228(1):129-41. doi: 10.1007/s00213-013-3017-9.
- 15. Eren I, Nazıroğlu M, Demirdaş A, Çelik Ö, Uğuz AC, Altunbaşak A, Özmen İ, Uz E Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochemi Res. 2007;32(3):497-505. doi: 10.1007/s11064-006-9258-9.
- 16. Lister INE, Ginting CN, Girsang E, Nataya ED, Azizah AM, Widowati W Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory, antinecrotic, antioxidant potency. Saudi Pharm J. 2020;28(10):1182-9. doi: 10.1016/j.jsps.2020.08.007.
- 17. Abdel-Wahab BA, Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav. 2011;100(1):59-65. doi: 10.1016/j.pbb.2011.07.015.
- 18. Yazğan Y, Yazğan B Gossypin Regulated Doxorubicin-Induced Oxidative Stress and Inflammation in H9c2 Cardiomyocyte Cells. Medical Records. 2024;6(1):44-9. doi:10.37990/medr.1383719.
- 19. Turner MD, Nedjai B, Hurst T, Pennington DJ Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563-2582. doi: 10.1016/j.bbamcr.2014.05.014.
- 20. Fraczek M, Kurpisz M Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa. J Androl. 2007;28(2):325-33. doi: 10.2164/jandrol.106.001149.
- 21. Yıldızhan K, Nazıroğlu M Glutathione depletion and parkinsonian neurotoxin MPP+-induced TRPM2 channel activation play central roles in oxidative cytotoxicity and inflammation in microglia. Mol Neurobiol. 2020;57(8):3508-25. doi: 10.1007/s12035-020-01974-7.
- 22. Korhonen R, Lahti A, Kankaanranta H, Moilanen E Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4(4):471-9. doi: 10.2174/1568010054526359.
- 23. Aktan F iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639-53. doi: 10.1016/j.lfs.2003.10.042.
- 24. Quincozes-Santos A, Bobermin LD, Latini A, Wajner M, Souza DO, Gonçalves C-A, Gottfried C Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PloS One. 2013;8(5):e64372. doi: 10.1371/journal.pone.0064372.
- 25. Giasson BI, Ischiropoulos H, Lee VM-Y, Trojanowski JQ The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer’s and Parkinson’s diseases. Free Radic Biol Med. 2002;32(12):1264-75. doi: 10.1016/s0891-5849(02)00804-3.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Cerrahi Onkoloji |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Nisan 2024 |
| Gönderilme Tarihi | 26 Mart 2024 |
| Kabul Tarihi | 23 Nisan 2024 |
| Yayımlandığı Sayı | Yıl 2024 Cilt: 8 Sayı: 1 |
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