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

Year 2022, , 97 - 103, 31.08.2022

İnci Turan , Salih Erdem , Meryem Ergenç Hale Sayan Özaçmak

https://doi.org/10.25048/tudod.1066739

Cited By: 1

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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