AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Hatice Fulya Yılmaz; Özlem Bozkurt Girit

Makale detayları

AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Yazarlar:

Hatice Fulya Yılmaz | Özlem Bozkurt Girit

Yayıncı:

Aydin Adnan Menderes University

Ana Başlıklar:

Animal Physiology - Biophysics | Peripheral Nervous System | Neurosciences (Other)

Dergi:

Meandros Medical And Dental Journal Vol.25 Issue 3, pp.317-336

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001327320

pISSN:

2149-9063

Anahtar kelimeler:

Özet:

 Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mgkgweek dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mgkg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the BaxBcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.

 Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mgkgweek dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mgkg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the BaxBcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.

 Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mgkgweek dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mgkg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the BaxBcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.

 Amaç: Kemoterapötik ajanlar nörodejeneratif değişiklere neden olabilmektedir. Bu çalışmada, bir nöromodülator olan agmatinin, siyatik sinirde metotreksat ile indüklenen nörodejenerasyon üzerine olan terapötik etkinliğinin araştırılması amaçlanmıştır. Materyal ve Metot: 40 adet erkek Wistar albino sıçan kontrol, metotreksat, agmatinin ve metotreksat-agmatinin olmak üzere dört deney grubuna ayrıldı. metotreksat uygulaması 3 hafta boyunca 37,5 mgkg dozda metotreksatin haftada bir kez intraperitonal yolla enjekte edilmesiyle gerçekleştirildi. agmatinin uygulaması ise 7 gün boyunca günde iki kez 40 mgkg dozda intraperitonal yolla enjekte edilerek gerçekleştirildi. Nosiseptif ağrı algısı, siyatik fonksiyonel indeks değişimleri ve davranış değişiklikleri analiz edildi. Sinir ileti hızı ölçümleri yapıldı. Siyatik sinirdeki apoptotik-mitofajik aktivite ile akson ve miyelin düzeyindeki histopatolojik değişimler incelendi. Bulgular: metotreksat uygulaması su labirenti testinde platforma kaçış süresinde uzamaya ve kadranda geçirilen sürede kısalmaya; açık alan testinde gezilen kare sayısında azalmaya ve nosiseptif ağrı algısında azalmaya neden oldu. metotreksat grubunda siyatik sinir iletim hızında azalma ve siyatik fonksiyon indeksi değerlerinde düşüş gözlemlendi. metotreksat uygulaması sonucu, siyatik sinirde artmış GFAP immünreaktivitesi ile azalmış akson çapı ve miyelin kalınlığı değerleri elde edildi. Ayrıca metotreksat gruplarında BaxBcl-2 protein ekspresyon oranının arttığı, Parkin protein ekspresyonunda ise değişim olmadığı gözlemlendi. metotreksat sonrasında uygulanan agmatinin, metotreksat grubuna kıyasla nosiseptif ağrı algısında, davranış performanslarında, sinir iletiminde, siyatik fonksiyon indeksi değerlerinde ve histopatolojik değişimlerde metotreksatin neden olduğu değişiklikleri iyileştirdi. Sonuç: Agmatinin, sıçan siyatik sinirinde metotreksat ile indüklenen periferal nöropatide tedavi edici potansiyele sahip olduğu görülmüştür.

Makale detayları

AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Yazarlar:

Hatice Fulya Yılmaz | Özlem Bozkurt Girit

Yayıncı:

Aydin Adnan Menderes University

Ana Başlıklar:

Animal Physiology - Biophysics | Peripheral Nervous System | Neurosciences (Other)

Dergi:

Meandros Medical And Dental Journal Vol.25 Issue 3, pp.317-336

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001327320

pISSN:

2149-9063

Methotrexate

Agmatine

Sciatic nerve

Peripheral neuropathyMetotreksat

Agmatin

Siyatik sinir

Periferal Nöropati

Sayı

Makale detayları

Yazarlar: Hatice Fulya Yılmaz | Özlem Bozkurt Girit

Yayıncı: Aydin Adnan Menderes University

Ana Başlıklar: Animal Physiology - Biophysics | Peripheral Nervous System | Neurosciences (Other)

Dergi: Meandros Medical And Dental Journal Vol.25 Issue 3, pp.317-336

Belge Tipi: Makale

Yayın Tarihi: 9/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001327320

pISSN: 2149-9063

Sayı

Yazarlar:

Hatice Fulya Yılmaz | Özlem Bozkurt Girit

Yayıncı:

Aydin Adnan Menderes University

Ana Başlıklar:

Animal Physiology - Biophysics | Peripheral Nervous System | Neurosciences (Other)

Dergi:

Meandros Medical And Dental Journal Vol.25 Issue 3, pp.317-336

Belge Tipi:

Makale

Yayın Tarihi:

9/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001327320

pISSN:

2149-9063