İn Vitro ve İn Vivo olarak oluşturulan deneysel diyabet modelinde Saksagliptin'in etkilerinin araştırılması
Küçük Resim Yok
Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Diyabet, insülin metabolizmasındaki bozulmalar sonucu gelişen kronik bir hastalıktır ve uzun süreli hiperglisemi diyabetik nöropatiye (DN) yol açmaktadır. Bu çalışmada, bir DPP-4 inhibitörü olan Saksagliptin'in (Sax) DN modellerindeki etkinliği değerlendirilmiştir. Materyal ve Metot: Çalışmada 40 adet Balb-c ırkı erkek fare kontrol, DN, DN+Sax-2 ve DN+Sax-10 olmak üzere 4 gruba ayrıldı (n=10). Kontrol dışındaki gruplara intraperitonal olarak tek doz streptozotosin (150mg/kg) enjekte edildi ve 21 gün süresince DN modeli oluşması için beklenildi. Kontrol grubuna bir uygulama yapılmazken, DN grubuna serum fizyolojik, DN+Sax-2 ve DN+Sax-10 gruplarına ise sırasıyla 2 ve 10mg/kg dozlarında Sax, oral gavaj yoluyla 15 gün süresince uygulandı. Bu süre boyunca farelerde nosiseptif davranış testleri (hot plate, tail flick, von Frey) gerçekleştirildi. 15.gün fareler dekapite edilerek pankreas ve kan dokuları toplandı. Çalışmanın in vitro basamağında ise 1-2 günlük Wistar Albino cinsi sıçanlardan dorsal kök gangliyonları (DKG) 24 saat yüksek glikoza maruz bırakıldı ve Sax'ın hücre canlılığına etkisi ile kullandığı hücresel yolak belirlendi. Elde edilen sonuçlar SPSS paket programında uygun istatistiksel yöntemler kullanılarak analiz edildi ve p<0.05 anlamlı kabul edildi. Bulgular: Sax'ın farelerde DN grubuna kıyasla ağrı eşiğini arttırdığı (p<0.05), antioksidan ve antiinflamatuar etkiler gösterdiği (p<0.05) ve pankreasın histolojik bütünlüğünü korumaya yardımcı olduğu belirlendi (p<0.05). Ayrıca Sax'ın DKG'de fosfoinositid-3 kinaz yolağını kullanarak hücre canlılığını arttırdığı tespit edildi (p<0.05). Sonuç: STZ kaynaklı diyabetik nöropatide, DPP-4 enzim inhibitörü olan Sax, terapötik potansiyel etkiler göstermektedir. Anahtar Kelimeler: Diyabet, DKG, Nöropatik Ağrı, Saksagliptin
Aim: Diabetes is chronic disease caused by impaired insulin metabolism and prolonged hyperglycemia leads to diabetic neuropathy (DN). In study, we evaluated efficacy of Saxagliptin (Sax), DPP-4 inhibitor, in DN models. Material and Method: In study, 40 Balb-c male mice were divided into 4 groups as control, DN, DN+Sax-2 and DN+Sax-10 (n=10). Groups except control were injected intraperitoneally with single dose of streptozotocin (150mg/kg) and waited for 21 days for formation of DN model. While no treatment was given to control group, saline was administered to DN group and Sax was administered to DN+Sax-2 and DN+Sax-10 groups at doses of 2 and 10mg/kg, respectively, by oral gavage for 15 days. During this period, nociceptive behavioral tests (hot plate, tail flick, von Frey) were performed. On 15th day, mice were decapitated, pancreas and blood tissues were collected. In in vitro step of study, dorsal root ganglia (DRG) of 1-2 day old Wistar Albino rats were exposed to high glucose for 24 hours and effect of Sax on cell viability and cellular pathway used were determined. Results were analyzed using appropriate statistical methods in SPSS package program and p<0.05 was considered significant. Results: It was determined Sax increased pain threshold (p<0.05), showed antioxidant and anti-inflammatory effects (p<0.05) and helped to maintain histological integrity of pancreas in mice compared to DN group (p<0.05). In addition, Sax was found to increase cell viability by utilizing phosphoinositide-3 kinase pathway in DRG (p<0.05). Conclusion: Sax, DPP-4 enzyme inhibitor, shows potential therapeutic effects in STZ-induced diabetic neuropathy. Key Words: Diabetes, DRG, Neuropathic Pain, Saxagliptin
Aim: Diabetes is chronic disease caused by impaired insulin metabolism and prolonged hyperglycemia leads to diabetic neuropathy (DN). In study, we evaluated efficacy of Saxagliptin (Sax), DPP-4 inhibitor, in DN models. Material and Method: In study, 40 Balb-c male mice were divided into 4 groups as control, DN, DN+Sax-2 and DN+Sax-10 (n=10). Groups except control were injected intraperitoneally with single dose of streptozotocin (150mg/kg) and waited for 21 days for formation of DN model. While no treatment was given to control group, saline was administered to DN group and Sax was administered to DN+Sax-2 and DN+Sax-10 groups at doses of 2 and 10mg/kg, respectively, by oral gavage for 15 days. During this period, nociceptive behavioral tests (hot plate, tail flick, von Frey) were performed. On 15th day, mice were decapitated, pancreas and blood tissues were collected. In in vitro step of study, dorsal root ganglia (DRG) of 1-2 day old Wistar Albino rats were exposed to high glucose for 24 hours and effect of Sax on cell viability and cellular pathway used were determined. Results were analyzed using appropriate statistical methods in SPSS package program and p<0.05 was considered significant. Results: It was determined Sax increased pain threshold (p<0.05), showed antioxidant and anti-inflammatory effects (p<0.05) and helped to maintain histological integrity of pancreas in mice compared to DN group (p<0.05). In addition, Sax was found to increase cell viability by utilizing phosphoinositide-3 kinase pathway in DRG (p<0.05). Conclusion: Sax, DPP-4 enzyme inhibitor, shows potential therapeutic effects in STZ-induced diabetic neuropathy. Key Words: Diabetes, DRG, Neuropathic Pain, Saxagliptin
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology
