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The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture

Year 2019, Volume: 16 Issue: 2, 86 - 91, 08.08.2019

Damla Binnetoğlu

https://doi.org/10.32707/ercivet.595655

Abstract

Agmatine is a newly found neurotransmitter and its role in important modulations of central nervous systems how the pharmacological importance of agmatine. The aim of this study was to investigate the possible toxic and proliferative effects of agmatine, which is known to have endogenous neuroprotective effect, on primary rat neuron culture. In this context, it has been tried to determine the possible toxic and protective effects of agmatine at 8 different exposure times at 5 different doses. Neuron cultures obtained from brain cortex in the neonatal rats are treated with agmatine at 15 min, 30 min, 1 h, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, doses of 10-2, 10-3, 10-4, 10-5 and 10-6 M. Then, the dose duration effect relationship was determined with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation kit. According to the results of the viability assay, a statistically significant neuroprotective effect was observed in 10-5 and 10-6 M doses, especially in 1 hour and 24 hours exposure periods. In addition, proliferation was observed only at a concentration of 10-4 M for 24 hours. However, no statistically significant difference in toxic effect was observed. Consequently agmatine showed neuroprotective effect in the primary rat neuron culture, especially at the lowest dose and the longest exposure.

References

  • 1. Alper N, Temiz A. Gıdalardaki biyojen aminler ve önemi. Türk Hij Den Biyo Derg 2001; 58(2): 71-80.
  • 2. Arıcıoğlu F. Agmatinin nöropskiyatrideki yeri. RCHP 2009; 3(1-2): 7-19.
  • 3. Binnetoglu D, Hacimuftuoglu A, Aricioglu F. Neuroprotective effects of agmatine in antineoplastic drugs induced neurotoxicity: In vitro study. Life Sci 2019; 221: 311-8.
  • 4. Binnetoğlu D, Yayla M. Agmatine and glutamate induced primary neuron damage: In vitro study. IRJPMS 2018; 2(1): 52-6
  • 5. Büyükuslu N, Eröz SE. Poliaminler ve kanser; Kanserli hastaların beslenmesinde poliaminlerin rolleri. MÜSBED 2015; 5(2); 123-8.
  • 6. Cetin D, Hacımuftuoglu A, Tatar A, Turkez H, Togar B. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology 2016; 68(4): 1361-7.
  • 7. Chen GG, Almeida D, Fiori L, Turecki G. Evidence of reduced agmatine concentrations in the cerebral cortex of suicides. Int J Neuropsychopharmacol 2018; 21(10): 895-900.
  • 8. Collins JD, Noerrung B, Budka H, Andreoletti O, Buncic S, Griffin J, Hald T, Havelaar A, Hope J, Klein G, Koutsoumanis K, McLauchlin J, Müller-Graf C, Nguyen-The C, Peixe L, Maradona MP, Ricci A, Sofos J, Threlfall J, Vågsholm I, Vanopdenbosch E. Scientific opinion on risk based control of biogenic amine formation in fermented foods. EFSA J 2011; 9(10): 2393-6.
  • 9. Dursun E, Gezen Ak D, Yılmazer S. Primer nöron kültürü tekniği. Maltepe Tıp Dergisi 2013; 5(2): 50-6.
  • 10. Fiori LM, Turecki G. Implication of the polyamine system in mental disorders. J Psychiatry Neurosci 2008; 33(2): 102-10.
  • 11. Gilad GM, Gilad VH. Accelerated functional recovery and neuroprotection by agmatine after spinalcord ischemia in rats. Neurosci Lett 2000; 296(2-3): 97-100.
  • 12. Grillo MA, Colombatto S. Metabolism and function in animal tissues of agmatine, biogenic amine from arginine. Amino Acids 2004; 26(1): 3-8.
  • 13. Gümrü S, Şahin C, Arıcıoğlu F. Yeni bir nörotransmitter/nöromodülatör olarak agmatine genel bir bakış. MÜSBED 2013; 3(1): 23-8.
  • 14. Hesterberg RS, Cleveland JL, Epling-Burnette PK. Role of polyamines in immune cell function. Med Sci 2018; 6(1): 22-41.
  • 15. Higgins D, Banker G. Primary dissociated cell cultures. In: Banker G, Goslin K, eds. Culturing Nerve Cells. Cambridge: MIT Press; 1998; pp. 37-79.
  • 16. Mayeur C, Veuillet G, Michaud M, Raul F, Blottiere HM, Blachier F. Effects of agmatine accumulation in human colon carcinoma cells on polyamine metabolism, DNA synthesis and the cell cycle. Biochimi Biophys Acta 2005; 1745 (1): 111-223.
  • 17. Piletz JE, Aricioglu F, Cheng JT, CA, Gilad VH, Haenisch B, Halaris A, Hong S, Le JE, Li J, Liı P, Molderings GJ, Rodrigues ALS, Satriano J, Seomg GJ, Wilcox G, Wu N, Gilad GM. Agmatine: Clinical application safter 100 years in translation. Drug Discov Today 2013; 18(17-18): 880-93.
  • 18. Reis D, Regunathan S. Is agmatine a novel neurotransmitter in brain? TIPS 2000; 21:187-93.
  • 19. Ulucan K, Uzbay, T. Gizli tehlike; Agmatin. ACU Sağlık Bil Derg 2016; (3):182-4.
  • 20. Uylaşer V, Konak A. Gıdalardaki biyojenaminler ve insan sağlığı açısından önemi. Gıda ve Yem Bilimi Teknolojisi 2004; 6; 26-33.
  • 21. Uzbay T, Kaya Yertutanol FT, Midi A, Cevreli B. Subkutaneous toxicity of agmatine in rats. Turk J Pharm Sci 2017; 14(2): 127-33.
  • 22. Uzbay T. Şizofreni tedavisinde yeni farmakolojik yaklaşımlar. Türk Psikiyatri Dergisi 2009; 20(2): 175-82.
  • 23. Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 2001; 64: 365-91.
  • 24. Zhu MY, Wang WP, Bissette G. Neuroprotective effects of agmatine aganist cell damage caused by glucocorticoids in cultured rat hippocampal neurons. Neuroscience 2006; 141 (4): 2019-27.

Sıçan Primer Nöron Kültüründe Agmatinin Doz-Süre-Etki Profili

Year 2019, Volume: 16 Issue: 2, 86 - 91, 08.08.2019

Damla Binnetoğlu

https://doi.org/10.32707/ercivet.595655

Abstract

Agmatinin yeni bir nörotransmitter adayı olması ve santral sinir sisteminde çok sayıda önemli modülasyonda görev alması farmakolojik önemini göstermektedir. Çalışmamızda endojen nöroprotektif etkisi olduğu bilinen agmatinin primer sıçan nöron kültüründe olası toksik ve proliferatif etkilerini ekzojen olarak araştırması amaçlanmıştır. Bu kapsamda agmatinin olası toksik ve protektif etkileri 5 farklı dozda ve 8 farklı maruziyet süresinde belirlenmeye çalışılmıştır. Yeni doğan sıçanların beyin korteksinden elde edilen nöron kültürlerine 10-2, 10-3, 10-4, 10-5 ve 10-6 M konsantrasyonda agmatin uygulanarak 15 dk, 30 dk, 1 saat, 2 saat, 4 saat, 8 saat, 12 saat ve 24 saat süre ile maruz bırakılmıştır. Daha sonra doz süre etki ilişkisini belirlemek için MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferasyon kiti kullanılmıştır. Yapılan canlılık testi analiz sonuçlarına göre 10-5 ve 10-6 M konsantrasyonda özellikle 1 saat ve 24 saat maruziyet sürelerinde istatistiksel olarak anlamlı nöroprotektif etki gözlenmiştir. Buna ilaveten sadece 10-4 M konsantrasyonda 24 saat maruziyet süresinde proliferasyon artışı gözlemlenmiştir. Ayrıca hiçbir zaman diliminde toksik etki gözlemlenememiştir. Sonuç olarak agmatin primer sıçan nöron kültüründe özellikle en düşük dozunda ve en uzun maruziyet süresinde nöroprotektif etki göstermiştir.

Keywords

Agmatin hücre ölümü nöronal kültür nöroproteksiyon

References

  • 1. Alper N, Temiz A. Gıdalardaki biyojen aminler ve önemi. Türk Hij Den Biyo Derg 2001; 58(2): 71-80.
  • 2. Arıcıoğlu F. Agmatinin nöropskiyatrideki yeri. RCHP 2009; 3(1-2): 7-19.
  • 3. Binnetoglu D, Hacimuftuoglu A, Aricioglu F. Neuroprotective effects of agmatine in antineoplastic drugs induced neurotoxicity: In vitro study. Life Sci 2019; 221: 311-8.
  • 4. Binnetoğlu D, Yayla M. Agmatine and glutamate induced primary neuron damage: In vitro study. IRJPMS 2018; 2(1): 52-6
  • 5. Büyükuslu N, Eröz SE. Poliaminler ve kanser; Kanserli hastaların beslenmesinde poliaminlerin rolleri. MÜSBED 2015; 5(2); 123-8.
  • 6. Cetin D, Hacımuftuoglu A, Tatar A, Turkez H, Togar B. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology 2016; 68(4): 1361-7.
  • 7. Chen GG, Almeida D, Fiori L, Turecki G. Evidence of reduced agmatine concentrations in the cerebral cortex of suicides. Int J Neuropsychopharmacol 2018; 21(10): 895-900.
  • 8. Collins JD, Noerrung B, Budka H, Andreoletti O, Buncic S, Griffin J, Hald T, Havelaar A, Hope J, Klein G, Koutsoumanis K, McLauchlin J, Müller-Graf C, Nguyen-The C, Peixe L, Maradona MP, Ricci A, Sofos J, Threlfall J, Vågsholm I, Vanopdenbosch E. Scientific opinion on risk based control of biogenic amine formation in fermented foods. EFSA J 2011; 9(10): 2393-6.
  • 9. Dursun E, Gezen Ak D, Yılmazer S. Primer nöron kültürü tekniği. Maltepe Tıp Dergisi 2013; 5(2): 50-6.
  • 10. Fiori LM, Turecki G. Implication of the polyamine system in mental disorders. J Psychiatry Neurosci 2008; 33(2): 102-10.
  • 11. Gilad GM, Gilad VH. Accelerated functional recovery and neuroprotection by agmatine after spinalcord ischemia in rats. Neurosci Lett 2000; 296(2-3): 97-100.
  • 12. Grillo MA, Colombatto S. Metabolism and function in animal tissues of agmatine, biogenic amine from arginine. Amino Acids 2004; 26(1): 3-8.
  • 13. Gümrü S, Şahin C, Arıcıoğlu F. Yeni bir nörotransmitter/nöromodülatör olarak agmatine genel bir bakış. MÜSBED 2013; 3(1): 23-8.
  • 14. Hesterberg RS, Cleveland JL, Epling-Burnette PK. Role of polyamines in immune cell function. Med Sci 2018; 6(1): 22-41.
  • 15. Higgins D, Banker G. Primary dissociated cell cultures. In: Banker G, Goslin K, eds. Culturing Nerve Cells. Cambridge: MIT Press; 1998; pp. 37-79.
  • 16. Mayeur C, Veuillet G, Michaud M, Raul F, Blottiere HM, Blachier F. Effects of agmatine accumulation in human colon carcinoma cells on polyamine metabolism, DNA synthesis and the cell cycle. Biochimi Biophys Acta 2005; 1745 (1): 111-223.
  • 17. Piletz JE, Aricioglu F, Cheng JT, CA, Gilad VH, Haenisch B, Halaris A, Hong S, Le JE, Li J, Liı P, Molderings GJ, Rodrigues ALS, Satriano J, Seomg GJ, Wilcox G, Wu N, Gilad GM. Agmatine: Clinical application safter 100 years in translation. Drug Discov Today 2013; 18(17-18): 880-93.
  • 18. Reis D, Regunathan S. Is agmatine a novel neurotransmitter in brain? TIPS 2000; 21:187-93.
  • 19. Ulucan K, Uzbay, T. Gizli tehlike; Agmatin. ACU Sağlık Bil Derg 2016; (3):182-4.
  • 20. Uylaşer V, Konak A. Gıdalardaki biyojenaminler ve insan sağlığı açısından önemi. Gıda ve Yem Bilimi Teknolojisi 2004; 6; 26-33.
  • 21. Uzbay T, Kaya Yertutanol FT, Midi A, Cevreli B. Subkutaneous toxicity of agmatine in rats. Turk J Pharm Sci 2017; 14(2): 127-33.
  • 22. Uzbay T. Şizofreni tedavisinde yeni farmakolojik yaklaşımlar. Türk Psikiyatri Dergisi 2009; 20(2): 175-82.
  • 23. Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 2001; 64: 365-91.
  • 24. Zhu MY, Wang WP, Bissette G. Neuroprotective effects of agmatine aganist cell damage caused by glucocorticoids in cultured rat hippocampal neurons. Neuroscience 2006; 141 (4): 2019-27.
There are 24 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Damla Binnetoğlu

Publication Date August 8, 2019
Submission Date March 26, 2019
Acceptance Date April 17, 2019
Published in Issue Year 2019 Volume: 16 Issue: 2

Cite

APA Binnetoğlu, D. (2019). The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 16(2), 86-91. https://doi.org/10.32707/ercivet.595655
AMA Binnetoğlu D. The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture. Erciyes Üniv Vet Fak Derg. August 2019;16(2):86-91. doi:10.32707/ercivet.595655
Chicago Binnetoğlu, Damla. “The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 16, no. 2 (August 2019): 86-91. https://doi.org/10.32707/ercivet.595655.
EndNote Binnetoğlu D (August 1, 2019) The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 16 2 86–91.
IEEE D. Binnetoğlu, “The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture”, Erciyes Üniv Vet Fak Derg, vol. 16, no. 2, pp. 86–91, 2019, doi: 10.32707/ercivet.595655.
ISNAD Binnetoğlu, Damla. “The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 16/2 (August 2019), 86-91. https://doi.org/10.32707/ercivet.595655.
JAMA Binnetoğlu D. The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture. Erciyes Üniv Vet Fak Derg. 2019;16:86–91.
MLA Binnetoğlu, Damla. “The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, vol. 16, no. 2, 2019, pp. 86-91, doi:10.32707/ercivet.595655.
Vancouver Binnetoğlu D. The Dose-Duration-Effect Profile of Agmatine on Rat Primary Neuron Cell Culture. Erciyes Üniv Vet Fak Derg. 2019;16(2):86-91.
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