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

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.