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Annals of Medicine and Surgery (2012) Jun 2024Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney... (Review)
Review
INTRODUCTION
Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney function, while chronic kidney disease involves a gradual deterioration lasting more than 3 months. Mechanisms of renal injury include impaired microcirculation, inflammation, and oxidative stress. Cysteinyl-leukotrienes (CysLTs) are inflammatory substances contributing to tissue damage. Montelukast, a leukotriene receptor antagonist, has shown potential renoprotective effects in experimental models of kidney injury.
METHODS
The authors conducted a scoping review using PubMed, Scopus, and Web of Science databases to identify relevant studies investigating the impact of montelukast on renal diseases. Articles published until 2022 were included and evaluated for quality. Data extraction and analysis were performed based on predetermined inclusion criteria.
RESULTS
The scoping review included 30 studies from 8 countries. Montelukast demonstrated therapeutic effects in various experimental models of nephrotoxicity and AKI induced by agents such as cisplatin, lipopolysaccharide, diclofenac, amikacin, , cyclosporine, methotrexate, cobalt-60 gamma radiation, doxorubicin, and cadmium. Studies involving human subjects with nephrotic syndrome, pyelonephritis, and other renal diseases also reported positive outcomes with montelukast treatment. Montelukast exhibited anti-inflammatory, anti-apoptotic, antioxidant, and neutrophil-inhibiting properties, leading to improved kidney function and histopathological changes.
CONCLUSIONS
Montelukast shows promise as a renoprotective medication, particularly in early-stage kidney injury. Its ability to mitigate inflammation, oxidative stress, and neutrophil infiltration contributes to its therapeutic effects. Further research is needed to explore the clinical applications and mechanisms underlying the renoprotective action of montelukast.
PubMed: 38846849
DOI: 10.1097/MS9.0000000000002085 -
Journal of Clinical Medicine Nov 2023Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and... (Review)
Review
Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and adverse consequences mainly due to intermittent hypoxemia. The pathogenesis of OSA is multifactorial. In children aged 2 years or older, adenoid and/or tonsil hypertrophy are the most common causes of upper airway lumen reduction; obesity becomes a major risk factor in older children and adolescents since the presence of fat in the pharyngeal soft tissue reduces the caliber of the lumen. Treatment includes surgical and non-surgical options. This narrative review summarizes the evidence available on the first-line approach in children with OSA, including clinical indications for medical therapy, its effectiveness, and possible adverse effects. Literature analysis showed that AT is the first-line treatment in most patients with adenotonsillar hypertrophy associated with OSA but medical therapy in children over 2 years old with mild OSA is a valid option. In mild OSA, a 1- to 6-month trial with intranasal steroids (INS) alone or in combination with montelukast with an appropriate follow-up can be considered. Further studies are needed to develop an algorithm that permits the selection of children with OSA who would benefit from alternatives to surgery, to define the optimal bridge therapy before surgery, to evaluate the long-term effects of INS +/- montelukast, and to compare the impact of standardized approaches for weight loss.
PubMed: 38002704
DOI: 10.3390/jcm12227092 -
Journal of Cutaneous Medicine and... Nov 2023Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch... (Review)
Review
IMPORTANCE
Prurigo nodularis (PN) is a debilitating inflammatory skin disease characterized by red to violaceous pruritic lesions. The goal of therapy is to break the scratch-itch cycle. Treatment varies and often requires a multimodal approach to target both immune and neural mediated aspects of disease.
OBJECTIVES
To review the efficacy of systemic treatment used to treat PN.
EVIDENCE REVIEW
A systematic search of keywords and Medical Subject Headings was performed in Ovid MEDLINE, Embase, Scopus, and ClinicalTrials.gov. The first 200 results of an abbreviated search in Google Scholar were also included. PRISMA guidelines were followed and the review was registered on PROSPERO (CRD42023412012). GRADE criteria were used to assess articles for quality of evidence.
FINDINGS
The search resulted in 1153 articles; 382 were duplicates, 643 were irrelevant, 19 were not retrieved, 21 were abstract only, and 88 are included in this review. There were 24 studies on dupilumab, 16 on thalidomide, 8 on cyclosporin, 7 on methotrexate, 3 each on lenalidomide and aprepitant, 2 each on alitretinoin, apremilast, baricitinib, gabapentin, intravenous (IV) immunoglobulins, pregabalin, tofacitinib, and 1 each on amitriptyline, azathioprine, butorphanol, isoquercitin, IV dexamethasone-cyclophosphamide/ oral cyclophosphamide, ketotifen, metronidazole, montelukast, nalbuphine, nemolizumab, serolopitant, tacrolimus, and herose derma zima capsule.
CONCLUSIONS AND RELEVANCE
Dupilumab reduces pruritus and appearance of lesions and is associated with the fewest number of side effects. Thalidomide and pregabalin are also effective, but their long-term use is limited by muscle and nerve pain. Janus Kinase inhibitors may be beneficial, but large population studies are lacking.
Topics: Humans; Thalidomide; Prurigo; Pregabalin; Cyclosporine; Pruritus; Cyclophosphamide
PubMed: 37987710
DOI: 10.1177/12034754231211797 -
Heliyon Nov 2023Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses...
Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.
PubMed: 38034763
DOI: 10.1016/j.heliyon.2023.e21842 -
Life Sciences Jul 2023Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast...
Montelukast prevents mice against carbon tetrachloride- and methionine-choline deficient diet-induced liver fibrosis: Reducing hepatic stellate cell activation and inflammation.
AIMS
Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis.
MATERIALS AND METHODS
Carbon tetrachloride (CCl) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays.
KEY FINDINGS
Chronic stimulation from CCl and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFβ/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation.
SIGNIFICANCE
Montelukast suppressed CCl- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Methionine; Hepatic Stellate Cells; Signal Transduction; Liver Cirrhosis; Liver; Fibrosis; Racemethionine; Inflammation; Diet; Transforming Growth Factor beta1
PubMed: 37178864
DOI: 10.1016/j.lfs.2023.121772 -
American Journal of Physiology. Lung... Aug 2023Asthma is one of the most common noncommunicable diseases in the world. Approximately 30% of severe cases are associated with fungal sensitization, often associated with...
Asthma is one of the most common noncommunicable diseases in the world. Approximately 30% of severe cases are associated with fungal sensitization, often associated with allergy to the opportunistic mold . Leukotrienes, immunopathogenic mediators derived from the metabolism of arachidonic acid (AA) by 5-lipoxygenase (5-LOX), are often elevated in severe asthma. As such, these mediators are Food and Drug Administration-approved therapeutic targets of the antiasthmatic drugs Zileuton/Zyflo and Singulair/Montelukast. A second enzyme involved in AA metabolism is 12/15-lipoxygenase (12/15-LOX; ). Here, C57BL/6 wild-type (WT) mice subjected to experimental fungal asthma had increased expression of mRNA and increased levels of 12-HETE, a product of 12/15-LOX activity, in the lung when compared with naïve and vehicle-treated mice. Mice deficient in 12/15-LOX () demonstrated better lung function, as measured by airway hyperresponsiveness (AHR), during fungal asthma. Histological assessment revealed reduced inflammation in the lungs of mice compared with WT mice, which was corroborated by flow cytometric analysis of multiple myeloid (eosinophils and neutrophils) and lymphoid (CD4+ T and γδ T) cell populations. This was further supported by decreased levels of specific chemokines that promote the recruitment of these cells. Likewise, type 1 and 2, but not type 17 cytokines, were significantly lower in the lungs of mice. Bone marrow chimera studies revealed that the presence of 12/15-LOX in hematopoietic cells contributed to AHR during fungal asthma. Taken together, our data support the hypothesis that hematopoietic-associated 12/15-LOX contributes to type 1 and 2 responses and exacerbation of allergic fungal asthma. Humans with asthma sensitized to fungi often have more severe asthma than those who are not sensitized to fungi. Products of arachidonic acid generated via 5-lipoxygenase are often elevated in severe asthma and are successful FDA-approved drug targets. Less understood is the role of products generated via 12/15-lipoxygenase. We demonstrate that 12/15-lipoxygenase expression in hematopoietic cells contributes to type 1 and 2 responses and impaired lung function during allergic fungal asthma.
Topics: Animals; Humans; Mice; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Asthma; Disease Models, Animal; Mice, Inbred C57BL; Mice, Knockout
PubMed: 37253655
DOI: 10.1152/ajplung.00090.2023 -
BMC Pulmonary Medicine Dec 2023This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in... (Meta-Analysis)
Meta-Analysis
An efficacy and safety evaluation of montelukast + fluticasone propionate vs. fluticasone propionate in the treatment of cough variant asthma in children: a meta-analysis.
PURPOSE
This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.
METHODS
Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I statistics, followed by sensitivity analysis and publication bias evaluation.
RESULTS
Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group.
CONCLUSION
Mon + Flu is effective and safe for the treatment of CVA in children.
Topics: Child; Humans; Acetates; Anti-Asthmatic Agents; Asthma; Cough; Cyclopropanes; Fluticasone; Quinolines
PubMed: 38053076
DOI: 10.1186/s12890-023-02721-z -
International Immunopharmacology Dec 2023Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic...
AIMS
Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic and testicular tissues is unknown. This study investigated the effect of CysLTR1 antagonism by montelukast on toll-like receptor (TLR)4 and nuclear factor kappa B (NF-κB) pathways in diabetes-induced aortic and testicular injury.
METHODS
Adult male Sprague-Dawley rats were made diabetic with Streptozotocin (STZ, 55 mg/kg). Following this, Streptozotocin-induced diabetic (SD) rats were administered montelukast (10 and 20 mg/kg, orally) for 8 weeks. Blood glucose, serum malondialdehyde (MDA), inflammatory markers, and histopathology were evaluated.
RESULTS
Montelukast showed protection against diabetic complications, as evidenced by the ameliorative effect against STZ-induced alterations in oxidative stress as indicated by serum MDA levels. Moreover, montelukast conferred a significant decrease in the aortic and testicular levels of CysLTR1, TLR4, and NF-κB with a subsequent decrease in the levels of NOD-like receptor family pyrin domain containing (NLRP)3, caspase 1, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α. Additionally, administration of montelukast resulted in autophagy stimulation, as shown by decreased p62/Sequestosome (SQSTM)1 levels. Finally, montelukast protection resulted in normal thickness of whole aortic wall, regular tunica (t.) intima, mild vacuolation of smooth muscle fibers in aorta, increased size of seminiferous tubules, and increased spermatogenesis in testis as demonstrated by histopathology.
CONCLUSIONS
The protective effect of montelukast against diabetes-induced aortic and testicular injury is due to its antioxidant, anti-inflammatory, and autophagy stimulation characteristics.
Topics: Rats; Male; Animals; NF-kappa B; Rats, Sprague-Dawley; Streptozocin; Diabetes Mellitus; Tumor Necrosis Factor-alpha; Inflammation; Diabetes Complications; Aorta
PubMed: 37907048
DOI: 10.1016/j.intimp.2023.111127 -
Medicina (Kaunas, Lithuania) Apr 2024: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. : The study was...
: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. : The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. : The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. : The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.
Topics: Sulfides; Cyclopropanes; Animals; Quinolines; Acetates; Rats, Wistar; Diabetes Mellitus, Experimental; Male; Rats; Lung; Pulmonary Fibrosis; Leukotriene Antagonists; Streptozocin; Blood Glucose
PubMed: 38792932
DOI: 10.3390/medicina60050749