title: The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.
abstract: There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25 mg/kg body weight) for 30 days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10 mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B4(LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.
authors.affiliation: Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. mahmoudmsaid@sci.asu.edu.eg.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Said
authors.affiliation: Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003521:Cyclopropanes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004958:Estradiol; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011472:Prostatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011804:Quinolines / Q000494:pharmacology*; D017208:Rats, Wistar; D018077:Receptors, Leukotriene / Q000187:drug effects* / Q000378:metabolism; D013440:Sulfides; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D003521:Cyclopropanes; D019040:E-Selectin; D018836:Inflammation Mediators; D015850:Interleukin-6; D020024:Leukotriene Antagonists; D016328:NF-kappa B; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C083169:leukotriene D4 receptor; C093875:montelukast
keywords: Chemokines; Cytokines; Leukotrienes; Montelukast; Nonbacterial prostatitis