montelukast and Cystitis--Interstitial

The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology.. Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis.. Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically.. Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment.. We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.

Topics: Animals; Cyclophosphamide; Cystitis, Interstitial; Female; Humans; Interleukin-6; Leukotriene Antagonists; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

What's known on the subject? and What does the study add? 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.. • 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.. • 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.. • 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.. • Montelukast appears to have a protective function in the bladder injury model via the anti-inflammatory effects of this leukotriene receptor antagonist.

Topics: Acetates; Animals; Cell Count; Cyclopropanes; Cystitis, Interstitial; Disease Models, Animal; Female; Glutathione; Glycosaminoglycans; Immunohistochemistry; Leukotriene Antagonists; Malondialdehyde; Mast Cells; Microscopy, Electron, Transmission; Protamines; Quinolines; Rats; Rats, Wistar; Sulfides; Tryptases; Urinary Bladder; Urothelium

To describe the effects of montelukast, a leukotriene receptor antagonist commonly used in the treatment of allergic rhinitis and asthma, on the symptoms of interstitial cystitis (IC).. A 64-year-old male had a history of IC with previous trials of solifenacin, dutasteride, and tamsulosin and little improvement in IC symptom reduction. When montelukast 10 mg was initiated for allergic rhinitis symptoms, a substantial improvement in urinary urgency and pain during therapy was noted. This improvement subsequently disappeared when montelukast was stopped.. IC, a rare occurrence in the male population, is related to an inflammatory process and has also been associated with inappropriate leukotriene release, which is the target of montelukast therapy. In general, treatment for IC includes systemic medical therapy, local bladder treatment, surgical and neurosurgical procedures, and intravesical drug installation. Currently, montelukast is Food and Drug Administration approved for use in the treatment and prevention of mild-to-moderate asthma and exercise-induced asthma, as well as treatment of seasonal and perennial allergic rhinitis. While montelukast treatment did not cure the patient's IC, it improved his quality of life through substantial symptomatic relief, including less pain and urgency.. Montelukast may be an effective treatment option in the management of interstitial cystitis. Further research is needed to substantiate this novel use.

Topics: Acetates; Cyclopropanes; Cystitis, Interstitial; Humans; Leukotriene Antagonists; Male; Middle Aged; Quality of Life; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides

Topics: Acetates; Cyclopropanes; Cystitis, Interstitial; Female; Humans; Leukotriene Antagonists; Pain; Pilot Projects; Quinolines; Sulfides; Urination Disorders

The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis.. Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales.. After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment.. Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.

Topics: Acetates; Aged; Cyclopropanes; Cystitis, Interstitial; Humans; Leukotriene Antagonists; Male; Mastocytosis; Middle Aged; Pilot Projects; Prospective Studies; Quinolines; Sulfides; Urinary Bladder Diseases