j. fac. pharm. ankara Journal of Faculty of Pharmacy of Ankara University 1015-3918 2564-6524 Ankara University 10.33483/jfpau.1507431 Pharmaceutical Sciences Basic Pharmacology Eczacılık Bilimleri Temel Farmakoloji VILDAGLIPTIN IMPROVES DETRUSOR CONTRACTILITY IN A MOUSE MODEL OF CYCLOPHOSPHAMIDE-INDUCED OVERACTIVE BLADDER VİLDAGLİPTİN, SİKLOFOSFAMİD İLE İNDÜKLENEN AŞIRI AKTİF MESANE FARE MODELİNDE DETRÜSÖR KONTRAKTİLİTESİNİ İYİLEŞTİRİR https://orcid.org/0000-0002-1982-7820 Engin Seçkin KARADENİZ TEKNİK ÜNİVERSİTESİ https://orcid.org/0000-0003-3284-848X Barut Elif Nur KARADENIZ TECHNICAL UNIVERSITY https://orcid.org/0000-0002-3073-3462 İsmailoğlu Karaca Merve KARADENIZ TECHNICAL UNIVERSITY https://orcid.org/0009-0005-1926-5644 Yanık Melis Nazlı KARADENIZ TECHNICAL UNIVERSITY 01 20 2025 49 1 53 61 06 30 2024 10 02 2024 Copyright © 1971, Journal of Faculty of Pharmacy of Ankara University 1971 Journal of Faculty of Pharmacy of Ankara University

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.

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.

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