Uroprotective effect of pantoprazole against cyclophosphamide-induced cystitis in mice.

Abstract

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 (300mg/kg) to induce HC. PPZ (20, 50, and 100mg/kg/day;i.p.) was administered for 3 consecutive days before the induction of HC. Mesna (30mg/kg;i.p.) was administered 20min before, 4 and 8h after CP injection to compare the protective effects of PPZ. After 24h 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 (100mg/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.