JPP 2007, 59: 837–842 © 2007 The Authors Received October 26, 2006 Accepted February 19, 2007 DOI 10.1211/jpp.59.6.0009 ISSN 0022-3573 837 Montelukast reduces ischaemia/reperfusion-induced bladder dysfunction and oxidant damage in the rat Göksel Sener, Ozer Sehirli, Hale Toklu, Feriha Ercan and Inci Alican Abstract The present study aimed to investigate the possible beneficial effects of the cysteinyl leukotriene-1 receptor antagonist montelukast on contractility and oxidant damage after ischaemia/reperfusion (I/R) of rat urinary bladder. The abdominal aorta of Sprague-Dawley rats was occluded to induce I/R. Montelukast (10 mg kg − 1 ) or saline was administered intraperitoneally before I/R. In the sham-oper- ated group, the abdominal aorta was left intact and the animals were treated with montelukast or saline. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for biochemical assays. In the I/R group, the isometric contractile responses of the bladder strips to carbachol (10 − 8 –10 − 4 M) were lower than those of the control group and were reversed by treatment with montelukast. Lipid peroxidation and myeloperoxidase activity of the bladder tissues in the I/R group were greater than in the sham-operated group. Montelukast treat- ment in the I/R group decreased these parameters compared with I/R alone. Similarly, the significant decrease in tissue glutathione level in the I/R group compared with controls was also prevented by montelukast. Treatment with montelukast almost completely reversed the low contractile responses of rat urinary bladder to carbachol and prevented oxidative tissue damage following I/R. Increasing evidence has suggested that bladder ischaemia as a result of a reduction of blood flow by surgical trauma could produce bladder dysfunction, such as a decrease in bladder contraction, compliance and capacity with increased post-voiding residual volume. Studies on preparations from whole bladder or bladder strips revealed significant bladder dysfunc- tion following hypoxia or ischaemia (Lin et al 1995; Bratslavsky et al 1999). Reperfusion and re-oxygenation of ischaemic tissue generates reactive oxygen metabolites that ca lipid peroxidation of cellular membranes, and alters various cellular functions (Levin et al 1998; Ohnishi et al 1998). Thus, free radical reduction for the treatment of ischaemia/reper- fusion (I/R) injury has found its first clinical application in the prevention of post-ischaemic organ dysfunction. Leukotrienes (LT) are eicosanoids that are generated via biochemical pathways cat lysed by lipoxygenase enzymes (Lewis & Austen 1984; Henderson 1994). They are compo- nents of the arachidonic acid cascade, which include prostaglandins, prostacyclins an thromboxanes, among other lipid mediators (Lewis & Austen 1984; Henderson 1994). Cysteinyl LTs (CysLTC4, D4 and E4) contract smooth muscles, particularly in the periph- eral airways, and are regarded as pivotal mediators of bronchial asthma. In the microcircula tion, they increase the permeability in post-capillary venules, which leads to extravasation of plasma. Thus, drugs that interfere with the biosynthesis and action of LTs have been mar keted as novel medications against asthma and allergic rhinitis (Drazen et al 1999). L have also been detected in serum, urine and renal tissue during glomerular inflammation (Lianos 1988; Lianos & Noble 1989; Yared et al 1991; Petric & Ford-Hutchison 1994). In this setting, they have been implicated as triggers for neutrophil recruitment and activation intrarenal vasoconstriction, mesangial cell contraction, and proliferation of resident glomeru lar cells (Badr et al 1984; Simonson & Dunn 1986; Badr et al 1987; Bresnahan et al 1992). Montelukast has a high affinity for the CysLT1 receptor and has been demonstrate to reduce the inflammatory response during the development of eosinophilic airway inflammation, possibly by inhibiting the release of pro-inflammatory mediators such a Introduction Marmara University, Faculty of Pharmacy, Department of Pharmacology, Haydarpasa, 34668, Istanbul, Turkey Göksel Sener, Ozer Sehirli, Hale Toklu Marmara University, School of Medicine, Department of Histology and Embryology, Haydarpasa, 34668, Istanbul, Turkey Feriha Ercan Marmara University, School of Medicine, Department of Physiology, Haydarpasa, 34668, Istanbul, Turkey Inci Alican Correspondence: Göksel Sener, Marmara University Faculty of Pharmacy, Department of Pharmacology, Haydarpasa, 34668, Istanbul, Turkey. E-mail: gsener@marmara.edu.tr