Ovarektomize Dişi Sıçanlarda 1,1-Dimetilbiguanit Hidroklorid (Metformin)'in Detrüsör Kas Kontraktil Yanıtı Üzerine Etkileri

Abstract

Amaç: Menopoz, yumurtalık foliküler rezervinin tükenmesi ve ardından adet döngüsünün durması olarak tanımlanır. Kadınlarda gonadal steroid hormonlarının mesane fonksiyonunda önemli rol oynadığı bildirilmiştir. Menopozun bir sonucu olarak idrar düzeninde değişiklikler meydana gelir. 1,1-dimetilbiguanid hidroklorür, metformin (MET), hepatik glukoz üretimini ve periferik insülin direncini azaltmak için kullanılan oral bir anti-diyabetik ilaçtır. Son zamanlarda yapılan çalışmalar, MET'in diyabetin neden olduğu mesane disfonksiyonunda koruyucu etkileri olduğunu ortaya koymuştur. Bu çalışmanın amacı, yumurtalıkları alınmış (OVX) dişi sıçanların detrusor kasılma fonksiyonunda MET'nin terapötik potansiyelini değerlendirmektir. Gereç ve Yöntemler: Endojen gonadal steroid sekresyonunu ortadan kaldırmak için bilateral ovariektomi yapıldı. Her grupta 8 hayvan olacak şekilde dört grup tasarlanmıştır: Kontrol, MET uygulanan kontrol, OVX ve MET uygulanan OVX grupları. MET (25 mg/kg) 14 gün boyunca oral gavaj yoluyla günlük olarak uygulandı. İzole mesane kas şeritlerinin kontraktil aktivitesi in vitro organ banyosunda değerlendirildi. Detrusor şeritlerinin kasılma yanıtları, farklı dozlarda karbakol (10-8-10-2M) ve purinerjik agonist ATP kullanılarak belirlendi. Striplerin gevşeme yanıtı izoproterenol ile değerlendirildi. Bulgular: Detrusor kas şeritlerinin 10-5-10-2 M dozlarda karbakole olan kontraktil yanıtları, OVX grubunda, kontrol ve MET ile tedavi edilen kontrol gruplarına kıyasla azaldı. MET tedavisi, 10-2 ve 10-3 M karbakol dozlarında OVX'in neden olduğu kasılma cevaplarındaki azalmayı kısmen tersine çevirdi. Deney grupları arasında gevşeme yanıtında istatistiksel olarak anlamlı bir fark yoktu. Sonuç: Bulgularımız, MET ile tedavinin postmenopozal kadınlarda mesane fonksiyon bozukluğuna karşı yeni potansiyel terapötik ajan olabileceğini düşündürmektedir. Menopozun neden olduğu detrusor disfonksiyonunda MET'nin terapötik potansiyeli için daha ileri çalışmalara ihtiyaç vardır.

Keywords

• Ovarektomi
• Detrusör kontraktilitesi
• Menopoz
• Metformin

The Effects of 1,1-Dimethylbiguanide Hydrochloride (Metformin) on Detrusor Muscle Contractile Response in Ovariectomized Female Rats

Abstract

Aim: Menopause is defined as the depletion of the ovarian follicular reserve followed by the cessation of menstrual cycles. It has been reported that gonadal steroid hormones play an important role in bladder function in women. Changes in urine pattern including overactive bladder, stress incontinence and recurrent urinary tract infections occur as a result of menopause. 1,1-dimethylbiguanide hydrochloride, metformin, (MET) is an oral anti-diabetic drug used to reduce hepatic glucose production and peripheral insulin resistance. Recent studies have revealed that MET has a protective effects in diabetes induced bladder dysfunction. The aim of this study was to test the therapeutic potential of MET in detrusor contractile function of ovariectomized (OVX) female rats. Material and Methods: Bilateral ovariectomy was performed to eliminate endogenous gonadal steroids secretion. Four groups are designed with 8 animals in each group: Control, MET-administered control, OVX, and MET-administered OVX groups. MET (25 mg/ kg) was administered daily by oral gavage for 14 days. Contractile activity of isolated bladder muscle strips were evaluated in vitro organ bath. The contractile responses of detrusor strips were determined using different doses of carbachol (10-8-10-2M) and purinergic agonist ATP. The relaxation response of strips were determined by isoproterenol Results: The contractile responses of detrusor muscle strips to carbachol at doses 10-5-10-2 M were decreased in the OVX group compared to control and MET treated control groups. MET treatment partially reversed the reduction in OVX-induced contractile responses at 10-2 and 10 -3 M carbachol doses. There were no statistically significant difference in relaxation response between the experimental groups. Conclusion: Our findings suggest that treatment with MET could be the new potential therapeutic agent against bladder dyfunction in postmenopausal women. Further studies are needed for the therapeutic potential of MET in detrusor dysfunction induced by menopause.

Keywords

• Ovariectomy
• Detrusor contractility
• Menopause
• Metformin

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