Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate-induced changes in rat urinary bladder

Abstract

The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry. OBJECTIVE To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl-containing leukotrienes, on protamine sulphate (PS)-induced changes in rat urinary bladder. MATERIALS AND METHODS Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h. In the PS-applied and ML-treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days. The urinary bladder was investigated for general morphology under a light microscope. Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry. RESULTS Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope. Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions. In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions. The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings. CONCLUSION Montelukast appears to have a protective function in the bladder injury model via the anti-inflammatory effects of this leukotriene receptor antagonist.