Akademik Veri Yönetim Sistemi
3rd International Gazi Pharma Symposium Series, Türkiye, 8 - 10 Eylül 2021, ss.68-69
Cyclophosphamide
(CP)-induced cystitis is a challenging clinical problem involving inflammation
and dysfunction of bladder (1). Trimetazidine (TMZ) is an anti-anginal drug with
anti-oxidant and anti-inflammatory properties (2). However, its effect on
CP-induced cystitis is unknown. We aimed to investigate the potential protective
effects of TMZ in CP-induced cystitis via inhibiting TLR4/NFκB pathway and its effect
on the anti-tumor activity of CP. Cystitis was induced by a single injection of
CP (300 mg/kg; i.p) in mice and TMZ was
administered (10 and 20 mg/kg/day; i.p.) for 5 consecutive days before CP. 24 hours
after cystitis induction, the bladders were removed for histopathological evaluation, functional contractility
studies, biochemical analysis and western blotting. Effect of TMZ on the
anti-tumor activity of CP was
evalauted in MDA-MB-231 cells with MTT assay (3,4). CP caused
severe cystitis confirmed by histological alterations, which was partially
ameliorated by TMZ. CP-induced cystitis caused a signifcant decrease in the carbachol-evoked
contractions of bladder strips and TMZ (20 mg/kg) pretreatment restored the
contractile response. SOD activity and GSH content –biomarkers of antioxidant status-
were significantly increased and, TNF-α and IL-1β levels –proinflammatory
cytokines- were markedly decreased in the bladders of TMZ-pretreated mice compared to CP. TMZ
reduced the CP-induced increase in TLR4 expression and NFκB phosphorylation in the
bladders. TMZ alone and CP co-treatment decreased the cell viability. Our study
provides the first evidence that TMZ attenuates CP-induced urotoxicity due to its
anti-oxidant and anti-inflammatory effects possibly via downregulating
TLR4/NFκB signaling while not inerfering with the anti-tumor activity of CP.