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GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA

Yıl 2019, Cilt: 7 Sayı: 3, 156 - 164, 18.12.2019

Damla Binnetoğlu Muhammed Yayla Tuğba Nurcan Yüksel

Öz

Amaç: Çalışmamızda eksitatör bir nörotransmitter
olan Glutamata bağlı nörotoksisitenin önlenmesi amacıyla güçlü antioksidan, antiinflamatuar
ve antiapoptotik olan Floretin ve Florizin’in etkilerini araştırmayı amaçladık.



Materyal ve Metot: Çalışmamızda yeni doğan sıçan korteksi
kullanıldı. Floretin ve Florizin 10-5 ve 2x10-5 M
konsantrasyonlarında uygulandıktan 2 saat sonra 6x10-3 ve 3x10-3 M
konsantrasyonlarında Glutamat uygulaması gerçekleştirildi. Glutamat
uygulamasından 6 saat sonra hücrelerden mRNA izolasyonu yapıldı. 24 saat sonra
ise MTT testi, total oksidan ve antioksidan kapasite ölçümleri
gerçekleştirildi.



Bulgular: Çalışmamızda Glutamat artan
dozlarda hücre canlılığını azaltırken Floretin ve Florizin uygulaması yüksek
dozda en iyi nöroprotektif etkiyi ortaya koydu. Toksisiteye bağlı artan total
oksidan kapasite Floretin ve Florizin tarafından anlamlı derecede düzeltildi. Toksisite
oluşturulan grupta azalan antioksidan kapasite Floretin ve Florizin uygulaması
ile düzelme gösterdi. Floretin ve Florizin tek başlarına uygulandığında hücre
canlılığını anlamlı derecede etkilemezken, antioksidan kapasiteyi artırdı, oksidan kapasiteyi ise azalttı.
Aynı zamanda Glutamat uygulaması sonrası artan TNF-α mRNA ekspresyonu, Floretin
ve Florizin uygulaması ile anlamlı derecede azaldı. Glutamata bağlı artan kaspaz
3 ve kaspaz 9 mRNA ekspresyonu ise Floretin ve Florizin uygulaması ile düzelme
gösterdi.



Sonuç: Bu bulgular, güçlü antioksidan,
antiinflamatuar ve antiapoptotik olan Floretin ve Florizin’in Glutamatın neden
olduğu nörotoksisitede koruyucu olabileceğini ve Glutamatın neden olduğu
nörolojik bozuklukların önlenmesi için terapötik ajanlar olarak
kullanılabileceğini gösterir.

Anahtar Kelimeler

Nörotoksisite Floretin Florizin Glutamat Hücre kültürü

Kaynakça

  • Shao X, Bai N, He K, Ho CT, Yang CS, Sang S. Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species. Chem Res Toxicol. 2008;21(10):2042-50.
  • Zhao Y, Liu C, Lai X, Hou S, Zeng X, Li X. Immunomodulatory activities of phlorizin metabolites in lipopolysaccharide-stimulated RAW264.7 cells. Biomed Pharmacother. 2017;91:49-53.
  • Duge de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D ve ark. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010;71(4):443-52.
  • Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res. Rev 2005;21(1):31-8.
  • Aşkın Görgülü, Talat Kırış. Eksitatör aminoasidler ve eksitotoksisite. Türk Nöroşir Derg. 2005;15(1): 33-38.
  • Ömer Faruk Aydın, Aslı Kurne, Rana Karabudak. MS patogenezinde basamaklar-II:nörodejenerasyonda biyolojik göstergeler, sodyum kanalları ve glutamatın rolü. Türk Nöroşir Derg. 2006;12(2):98-105.
  • Sharma A, Kaur G. Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med. 2018;18(1):268.
  • Li JM, Zeng YJ, Peng F, Li L, Yang TH, Hong Z ve ark. Aberrant glutamate receptor 5 expression in temporal lobe epilepsy lesions. Brain Res. 2010;1311:166-74.
  • Hirata Y, Yamamoto H, Atta MS, Mahmoud S, Oh-hashi K, Kiuchi K. Chloroquine inhibits glutamate-induced death of a neuronal cell line by reducing reactive oxygen species through sigma-1 receptor. J Neurochem. 2011;119(4):839-47.
  • Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH ve ark. Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett. 2011;499(3):181-5.
  • Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking. Clin Biochem. 2014;47(6):393-7.
  • Nampoothiri M, Reddy ND, John J, Kumar N, Kutty Nampurath G, Rao Chamallamudi M. Insulin blocks glutamate-induced neurotoxicity in differentiated SH-SY5Y neuronal cells. Behav Neurol. 2014;2014:674164.
  • Wang G, Gao Y, Wang H, Wang J, Niu X. Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism. Appl Microbiol Biotechnol. 2018;102(24):10665-74.
  • Xu M, Gu W, Shen Z, Wang F. Anticancer Activity of Phloretin Against Human Gastric Cancer Cell Lines Involves Apoptosis, Cell Cycle Arrest, and Inhibition of Cell Invasion and JNK Signalling Pathway. Med Sci Monit. 2018;24:6551-58.
  • Cho SJ, Moon JS, Lee CM, Choi AM, Stout-Delgado HW. Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis. Am J Respir Cell Mol Biol. 2017;56(4):521-31.
  • Puel C, Quintin A, Mathey J, Obled C, Davicco MJ, Lebecque P ve ark. Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions. Calcif Tissue Int. 2005;77(5):311-8.
  • Barreca D, Curro M, Bellocco E, Ficarra S, Laganà G, Tellone E ve ark. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors. 2017;43(4):549-57.
  • Ullen A, Fauler G, Bernhart E, Nusshold C, Reicher H, Leis HJ ve ark. Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro. Free Radic Biol Med. 2012;53(9):1770-81.
  • Chaparro-Huerta V, Flores-Soto ME, Gudino-Cabrera G, Rivera-Cervantes MC, Bitzer-Quintero OK, Beas-Zarate C. Role of p38 MAPK and pro-inflammatory cytokines expression in glutamate-induced neuronal death of neonatal rats. Int J Dev Neurosci. 2008;26(5):487-95.
  • Smith T, Groom A, Zhu B, Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med. 2000;6(1):62-6.
  • 21. Chang WT, Huang WC, Liou CJ. Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages. Food Chem. 2012;134(2):972-9.
  • 22. Rajabian A, Boroushaki MT, Hayatdavoudi P, Sadeghnia HR. Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells. DNA Cell Biol. 2016;35(11):666-79.
  • 23. Wang YC, Lee CM, Lee LC, Tung LC, Hsieh-Li HM, Lee-Chen GJ ve ark. Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12). J Biol Chem. 2011;286(24):21742-54.
  • 24. Kirkland RA, Saavedra GM, Cummings BS, Franklin JL. Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases. J Neurosci. 2010;30(48):16114-27.
  • 25. Choi BM, Chen XY, Gao SS, Zhu R, Kim BR. Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells. Pharmacol Rep. 2011;63(3):708-16.

Yıl 2019, Cilt: 7 Sayı: 3, 156 - 164, 18.12.2019

Damla Binnetoğlu Muhammed Yayla Tuğba Nurcan Yüksel

Öz

Kaynakça

  • Shao X, Bai N, He K, Ho CT, Yang CS, Sang S. Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species. Chem Res Toxicol. 2008;21(10):2042-50.
  • Zhao Y, Liu C, Lai X, Hou S, Zeng X, Li X. Immunomodulatory activities of phlorizin metabolites in lipopolysaccharide-stimulated RAW264.7 cells. Biomed Pharmacother. 2017;91:49-53.
  • Duge de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D ve ark. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010;71(4):443-52.
  • Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res. Rev 2005;21(1):31-8.
  • Aşkın Görgülü, Talat Kırış. Eksitatör aminoasidler ve eksitotoksisite. Türk Nöroşir Derg. 2005;15(1): 33-38.
  • Ömer Faruk Aydın, Aslı Kurne, Rana Karabudak. MS patogenezinde basamaklar-II:nörodejenerasyonda biyolojik göstergeler, sodyum kanalları ve glutamatın rolü. Türk Nöroşir Derg. 2006;12(2):98-105.
  • Sharma A, Kaur G. Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med. 2018;18(1):268.
  • Li JM, Zeng YJ, Peng F, Li L, Yang TH, Hong Z ve ark. Aberrant glutamate receptor 5 expression in temporal lobe epilepsy lesions. Brain Res. 2010;1311:166-74.
  • Hirata Y, Yamamoto H, Atta MS, Mahmoud S, Oh-hashi K, Kiuchi K. Chloroquine inhibits glutamate-induced death of a neuronal cell line by reducing reactive oxygen species through sigma-1 receptor. J Neurochem. 2011;119(4):839-47.
  • Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH ve ark. Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett. 2011;499(3):181-5.
  • Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking. Clin Biochem. 2014;47(6):393-7.
  • Nampoothiri M, Reddy ND, John J, Kumar N, Kutty Nampurath G, Rao Chamallamudi M. Insulin blocks glutamate-induced neurotoxicity in differentiated SH-SY5Y neuronal cells. Behav Neurol. 2014;2014:674164.
  • Wang G, Gao Y, Wang H, Wang J, Niu X. Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism. Appl Microbiol Biotechnol. 2018;102(24):10665-74.
  • Xu M, Gu W, Shen Z, Wang F. Anticancer Activity of Phloretin Against Human Gastric Cancer Cell Lines Involves Apoptosis, Cell Cycle Arrest, and Inhibition of Cell Invasion and JNK Signalling Pathway. Med Sci Monit. 2018;24:6551-58.
  • Cho SJ, Moon JS, Lee CM, Choi AM, Stout-Delgado HW. Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis. Am J Respir Cell Mol Biol. 2017;56(4):521-31.
  • Puel C, Quintin A, Mathey J, Obled C, Davicco MJ, Lebecque P ve ark. Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions. Calcif Tissue Int. 2005;77(5):311-8.
  • Barreca D, Curro M, Bellocco E, Ficarra S, Laganà G, Tellone E ve ark. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors. 2017;43(4):549-57.
  • Ullen A, Fauler G, Bernhart E, Nusshold C, Reicher H, Leis HJ ve ark. Phloretin ameliorates 2-chlorohexadecanal-mediated brain microvascular endothelial cell dysfunction in vitro. Free Radic Biol Med. 2012;53(9):1770-81.
  • Chaparro-Huerta V, Flores-Soto ME, Gudino-Cabrera G, Rivera-Cervantes MC, Bitzer-Quintero OK, Beas-Zarate C. Role of p38 MAPK and pro-inflammatory cytokines expression in glutamate-induced neuronal death of neonatal rats. Int J Dev Neurosci. 2008;26(5):487-95.
  • Smith T, Groom A, Zhu B, Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med. 2000;6(1):62-6.
  • 21. Chang WT, Huang WC, Liou CJ. Evaluation of the anti-inflammatory effects of phloretin and phlorizin in lipopolysaccharide-stimulated mouse macrophages. Food Chem. 2012;134(2):972-9.
  • 22. Rajabian A, Boroushaki MT, Hayatdavoudi P, Sadeghnia HR. Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells. DNA Cell Biol. 2016;35(11):666-79.
  • 23. Wang YC, Lee CM, Lee LC, Tung LC, Hsieh-Li HM, Lee-Chen GJ ve ark. Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12). J Biol Chem. 2011;286(24):21742-54.
  • 24. Kirkland RA, Saavedra GM, Cummings BS, Franklin JL. Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases. J Neurosci. 2010;30(48):16114-27.
  • 25. Choi BM, Chen XY, Gao SS, Zhu R, Kim BR. Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells. Pharmacol Rep. 2011;63(3):708-16.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Araştırma Makalesi
Yazarlar

Damla Binnetoğlu

Muhammed Yayla Bu kişi benim

Tuğba Nurcan Yüksel 0000-0001-5092-1674

Yayımlanma Tarihi 18 Aralık 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 7 Sayı: 3

Kaynak Göster

APA Binnetoğlu, D., Yayla, M., & Yüksel, T. N. (2019). GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA. Namık Kemal Tıp Dergisi, 7(3), 156-164.
AMA Binnetoğlu D, Yayla M, Yüksel TN. GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA. NKMJ. Aralık 2019;7(3):156-164.
Chicago Binnetoğlu, Damla, Muhammed Yayla, ve Tuğba Nurcan Yüksel. “GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA”. Namık Kemal Tıp Dergisi 7, sy. 3 (Aralık 2019): 156-64.
EndNote Binnetoğlu D, Yayla M, Yüksel TN (01 Aralık 2019) GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA. Namık Kemal Tıp Dergisi 7 3 156–164.
IEEE D. Binnetoğlu, M. Yayla, ve T. N. Yüksel, “GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA”, NKMJ, c. 7, sy. 3, ss. 156–164, 2019.
ISNAD Binnetoğlu, Damla vd. “GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA”. Namık Kemal Tıp Dergisi 7/3 (Aralık 2019), 156-164.
JAMA Binnetoğlu D, Yayla M, Yüksel TN. GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA. NKMJ. 2019;7:156–164.
MLA Binnetoğlu, Damla vd. “GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA”. Namık Kemal Tıp Dergisi, c. 7, sy. 3, 2019, ss. 156-64.
Vancouver Binnetoğlu D, Yayla M, Yüksel TN. GLUTAMAT İLE İNDÜKLENEN NÖRON HASARINDA FLORETİN VE FLORİZİN’İN ETKİLERİ: İN VİTRO ÇALIŞMA. NKMJ. 2019;7(3):156-64.
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