Dimetil Fumarat Streptozotosin ile Diyabet Oluşturulmuş Sıçanlarda Detrüsör Kontraktilitesini İyileştirir

Year 2024, Volume: 8 Issue: 3, 287 - 293, 30.12.2024

Seçkin Engin , Yeşim Kaya Yaşar , Elif Nur Barut

Abstract

potansiyel etkisi araştırıldı.
Gereç ve Yöntemler: Yetişkin erkek Sprague Dawley sıçanlara diyabet indüksiyonu için tek doz intraperitoneal streptozotosin (60 mg/
kg) verildi. Sekiz hafta sonra, diyabetik ve diyabetik olmayan sıçanlara dört hafta boyunca oral DMF (25 veya 100 mg/kg/gün) veya
taşıyıcı tedavileri uygulandı. Diyabet indüksiyonundan 12 hafta sonra, her bir sıçanın detrüsör şeritleri üzerinde in vitro organ banyosu
çalışmaları yapıldı ve şeritlerin KCl ve karbakol (CCh) ile indüklenen kasılma yanıtları değerlendirildi.
Bulgular: Detrüsör şeritlerinin KCl (80 mM) ve CCh ile indüklenen maksimum kasılma yanıtları, diyabetik grupta (sırasıyla 84,35±13,56
ve 178,80±29,66 mg gerim/mg doku) kontrol grubuna (sırasıyla 175,10±13,42 ve 399,40±77,63 mg gerim/mg doku) göre önemli ölçüde
azaldı (p<0,05). Ayrıca, DMF (4 hafta boyunca, 100 mg/kg/gün) tedavisi, diyabetik sıçanlarda KCl (158,20±25,82 mg gerim/mg doku) ve
CCh (342,50±42,86 mg gerim/mg doku) ile indüklenen bozulmuş maksimum kasılma yanıtlarını düzeltti; ancak 25 mg/kg dozda DMF
tedavisi hiçbir etki göstermedi.
Sonuç: Preklinik çalışmamızın sonuçları, DMF'nin diyabetle ilişkili mesane fonksiyon bozukluğunun tedavisinde umut verici bir
terapötik olarak yeniden konumlandırma potansiyeline sahip olduğunu göstermektedir

Keywords

Detrüsör kası, Dimetil fumarat, Diyabetik komplikasyon, Karbakol, Kasılma, Mesane, Streptozotosin

Dimethyl Fumarate Improves Detrusor Contractility in Streptozotocin-Induced Diabetic Rats

Abstract

Aim: The present study aimed to investigate potential effect of dimethyl fumarate (DMF) on bladder dysfunction in streptozotocin
(STZ)-induced diabetic rats.
Material and Methods: Adult male Sprague Dawley rats were given a single intraperitoneal dose of streptozotocin (60 mg/kg) to induce
diabetes. After eight weeks, diabetic and nondiabetic rats were orally treated with DMF (25 or 100 mg/kg/day) or vehicle for four weeks
orally. At 12 week after diabetes induction, in vitro organ bath studies were performed on detrusor strips of each rat and the contractile
responses to KCl and carbachol (CCh) of the strips were evaluated.
Results: The maximal KCl (80 mM)- and CCh-induced contractile responses of detrusor strips significantly (p<0.05) reduced in
diabetic group (84.35±13.56 and 178.80±29.66 mg tension/mg tissue, respectively) compared to the control group (175.10±13.42
and 399.40±77.63 mg tension/mg tissue, respectively). Moreover, DMF (100 mg/kg/day for 4 weeks) restored the impaired maximal
contractile responses to KCl (158.20±25.82 mg tension/mg tissue) and CCh (342.50±42.86 mg tension/mg tissue) in diabetic rats, but
DMF at 25 mg/kg had no effect.
Conclusion: The results of our preclinical study suggest that DMF has the potential to be repurposed as a promising therapeutic for the
treatment of diabetes-associated bladder dysfunction.

Keywords

Bladder, Carbachol, Contraction, Detrusor muscle, Diabetic complication, Dimethyl fumarate, Streptozotocin

Ethical Statement

All animal protocols were approved by the Institutional Animal Care and Use Committee of Karadeniz Technical University.

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