Uroprotective effect of pantoprazole against cyclophosphamide-induced cystitis in mice
The aim of the present study was to evaluate the potential uroprotective effect of pantoprazole (PPZ) in a mouse model of cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) due to its antioxidant and anti-inflammatory properties.
Balb/c mice received a single intraperitoneal (i.p.) injection of CP (300 mg/kg) to induce HC. PPZ (20, 50, and 100 mg/kg/day;i.p.) was administered for 3 consecutive days before the induction of HC. Mesna (30 mg/kg;i.p.) was administered 20 min before, 4 and 8 h after CP injection to compare the protective effects of PPZ. After 24 h of HC induction, the bladders were removed for functional studies, biochemical analyses, and histopathological examination.
In vitro contractility studies demonstrated that CP-induced HC decreased the responsiveness of detrusor muscle strips to acetylcholine (ACh), which was reversed by PPZ pretreatment at all doses tested. However, mesna treatment was not able to improve responsiveness to ACh. Biochemical analyses showed that CP caused significant elevation of malondialdehyde (MDA), reduction of total glutathione (GSH), and increment of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) level, which were measured in bladder homogenates. PPZ pretreatment at three doses found to be effective in reducing the CP-induced elevation of MDA and TNF-α levels. The highest dose of PPZ (100 mg/kg) caused a significant increase in GSH level. CP induced severe HC with marked bladder edema and histological disturbances which were partially abolished by PPZ pretreatment.
Our results indicate that PPZ pretreatment could attenuate CP-induced HC by interfering with oxidative stress and modulating proinflammatory cytokines.
KeywordsAntioxidant Cyclophosphamide Detrusor contractility Hemorrhagic cystitis Pantoprazole Proinflammatory cytokine
This study was supported by a grant from the Scientific Research Project Coordination Unit of Karadeniz Technical University (Project no. THD-2018-7356).
Compliance with ethical standards
The experimental protocol was approved by the Local Ethics Committee of Faculty of Medicine (protocol approval number: 2016/29) as Institutional Review Board. All animal studies were performed according to the Guide for the Care and Use of Laboratory Animals.
Conflict of interest
The authors declare that they have no conflict of interest.
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