VILDAGLIPTIN IMPROVES DETRUSOR CONTRACTILITY IN A MOUSE MODEL OF CYCLOPHOSPHAMIDE-INDUCED OVERACTIVE BLADDER

Öz

Objective: Overactive bladder (OAB) is a common urological disorder associated with detrusor overactivity linked to local tissue inflammation resulting in bladder hypersensitivity. The present study was aimed to investigate the therapeutic potential of vildagliptin (VIL), an anti-diabetic drug with anti-inflammatory effects, in a mouse model of cyclophosphamide (CP)-induced OAB. Material and Method: To induce an animal model of OAB, female Balb/c mice were intraperitoneally (i.p) injected with CP (80 mg/kg) every two days for 7 days. Then, mice were orally treated with saline (OAB model), VIL (10 or 50 mg/kg/day) or solifenacin (10 mg/kg/day) for 7 consecutive days. On the 17th day of experiment, organ-bath experiments were performed using isolated mouse detrusor muscle to evaluate tissue contractility. In another set of mice, bladder inflammation was assessed by Evans blue extravasation. Result and Discussion: Carbachol-induced contraction of detrusor strips significantly increased in OAB mice, which was reversed by treatment with VIL at 50 mg/kg or solifenacin. In addition, VIL treatment (50 mg/kg) reduced relative bladder weight and Evans blue dye extravasation into the bladders in CP-injected mice, demonstrating the inhibitory effect of VIL on CP-induced bladder inflammation. Our results showed that VIL ameliorated detrusor overactivity in a mouse model of CP-induced OAB by partially suppressing bladder inflammation.

Anahtar Kelimeler

• Bladder inflammation
• detrusor
• evans blue
• overactive bladder
• solifenacin
• vildagliptin

VİLDAGLİPTİN, SİKLOFOSFAMİD İLE İNDÜKLENEN AŞIRI AKTİF MESANE FARE MODELİNDE DETRÜSÖR KONTRAKTİLİTESİNİ İYİLEŞTİRİR

Öz

Amaç: Aşırı aktif mesane (AAM), mesane aşırı duyarlılığına neden olan lokal doku inflamasyonuna bağlı detrüsör aşırı aktivitesi ile ilişkili yaygın bir ürolojik bozukluktur. Bu çalışma, siklofosfamid SFD) ile indüklenen AAM fare modelinde, anti-inflamatuar etkili anti-diyabetik bir ilaç olan vildagliptinin (VIL) terapötik potansiyelini araştırmayı amaçlamıştır. Gereç ve Yöntem: AAM modelini indüklemek için dişi Balb/c farelere intraperitoneal olarak (i.p) 7 gün boyunca her iki günde bir SFD (80 mg/kg) enjekte edildi. Daha sonra fareler, art arda 7 gün boyunca oral olarak serum fizyolojik (AAM modeli), VIL (10 veya 50 mg/kg/gün) veya solifenasin (10 mg/kg/gün) ile tedavi edildi. Deneyin 17. gününde, mesane kontraktilitesini değerlendirmek için izole fare detrüsör kası kullanılarak organ banyosu deneyleri yapıldı. Başka bir fare grubunda mesane inflamasyonu, Evans mavisi ekstravazasyonu ile değerlendirildi. Sonuç ve Tartışma: Karbakol ile indüklenen detrüsör kasılması, AAM modeli farelerinde önemli ölçüde arttı ve bu artış, VIL (50 mg/kg) veya solifenasin tedavisi ile düzeldi. Ayrıca; VIL tedavisi (50 mg/kg), SFD enjekte edilmiş farelerde rölatif mesane ağırlığını ve Evans mavi boyasının mesanelere ekstravazasyonunu azalttı. Bu sonuç, VIL'in SFD kaynaklı mesane inflamasyonu üzerindeki inhibitör etkisini ortaya koydu. Sonuçlarımız, VIL’in mesane inflamasyonunu kısmen baskılayarak SFD kaynaklı bir AAM fare modelinde detrüsör aşırı aktivitesini iyileştirdiğini ortaya koydu.

Anahtar Kelimeler

• Aşırı aktif mesane
• detrusor
• evans mavisi
• mesane inflamasyonu
• solifenasin
• vildagliptin

Kaynakça

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