Akademik Veri Yönetim Sistemi
4th WG meeting, MuTaLig COST Action, İzmir, Türkiye, 5 - 06 Mart 2020
Trimetazidine (TMZ) is a novel anti-ischemic agent. This effect is mediated via inhibition of fatty acid oxidation and
improvement of myocardial energy metabolism (1). Both metabolic and cytoprotective effects of TMZ in cardiac
tissue has been extensively studied, however, its effects on other muscle tissue and potential therapeutic utility is
unknown (2). The aim of our project is to critically evaluate the actions of TMZ on mouse bladder contractility and
mouse model of cyclophosphamide (CP) - induced inflammation. To investigate the effect of TMZ on contractility,
detrusor smooth muscle strips were obtained from male Balb/c mice (25-35 grams), and changes in isometric tension
was recorded. TMZ pretreatment (300-1000 µM) attenuated carbachol- and KCI- induced contractions (p<0.05). TMZ
(10-1000 µM) induced a concentration-dependent relaxation in KCl-pre-contracted strips (Emax=66.50±3.48).
Incubation of detrusor strips with BaCl2 (Kir channel blocker) significantly decreased TMZ-induced relaxation whereas
incubation of tetraethylammonium, glibenclamide, and 4-aminopyridine had no effect. TMZ pretreatment (300-1000
µM) significantly inhibited CaCl2-induced contraction in Ca2+
-free Krebs solution, also reduced the contractile response
to carbachol in the presence of nifedipine. To investigate the cytoprotective effects of TMZ, hemorrhagic cystitis was
induced with CP (300 mg/kg, ip) and TMZ (10 and 20 mg/kg/day, ip; treatment) or vehicle (control) was applied for 3
consecutive days before CP. TMZ (20 mg/kg) prevented CP-induced histopathologic alterations. Collectively, our
results demonstrate that TMZ inhibits detrusor contractility via affecting intracellular calcium release and by inhibiting
Kir channels. Non-vascular smooth muscle relaxation and cytoprotective effect of TMZ suggest that this novel
molecule has a potential for repurposing/repositioning for bladder dysfunction and diseases.