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American Journal of Translational... 2023This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil...
OBJECTIVE
This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil (EOS) percentage in children comorbid with allergic rhinitis (AR) and asthma.
METHODS
The medical records of 114 children comorbid with AR and asthma treated in the Guizhou Provincial People's Hospital from February 2020 to September 2022 were collected and analyzed retrospectively. Among them, 54 children treated with budesonide were assigned to a control group, and the remaining 60 children treated with montelukast sodium combined with budesonide were assigned to an observation group. The efficacy was compared between the two groups. Additionally, the changes in pulmonary function, serum IgE levels, and EOS percentage were compared between the two groups before and after treatment (one month). The adverse reactions during the treatment and the recurrence of AR within 3 months were recorded. Logistics regression was conducted to analyze the risk factors affecting the efficacy in children.
RESULTS
The observation group showed a significantly higher overall response rate than the control group (P<0.05). After treatment, the observation group showed significantly higher levels of forced expiratory volume in 1 second (FEV1)%, FEV1/forced vital capacity (FVC), and peak expiratory flow (PEF) than the control group (P<0.05), and significantly lower IgE levels and EOS percentage than the control group (P<0.05). No significant difference was found between the two groups in terms of the total incidence of adverse reactions (P>0.05). According to the follow-up results of prognosis, the observation group presented a greatly lower recurrence rate of AR within 3 months than the control group (P<0.05). Multivariate logistics regression analysis showed that therapeutic regimen, IgE, and EOS were independent risk factors affecting the efficacy in the patients (P<0.05).
CONCLUSION
Montelukast sodium combined with budesonide can substantially improve the pulmonary function in children with comorbid AR and asthma, alleviate their symptoms of asthma and rhinitis, and lower the IgE level and EOS percentage. In addition, therapeutic regimen, IgE and EOS are independent risk factors affecting the efficacy in patients.
PubMed: 38186993
DOI: No ID Found -
Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats.Frontiers in Immunology 2022Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in...
BACKGROUND
Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.
OBJECTIVE
This study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats.
METHODS
Depression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2.
RESULTS
Overall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent.
CONCLUSION
Contrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment.
Topics: Acetates; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Cyclopropanes; Depression; Dimethyl Sulfoxide; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Prostaglandins; Quinolines; Rats; Sucrose; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36148246
DOI: 10.3389/fimmu.2022.981440 -
Viruses Apr 2022Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of...
Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.
Topics: Acetates; Animals; Coronavirus OC43, Human; Cyclopropanes; Middle East Respiratory Syndrome Coronavirus; Quinolines; SARS-CoV-2; Sulfides; COVID-19 Drug Treatment
PubMed: 35632604
DOI: 10.3390/v14050861 -
Drug Design, Development and Therapy 2014Asthma is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on avoidance... (Review)
Review
Asthma is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on avoidance of triggers such as food and aeroallergens, the use of inhaled bronchodilators/corticosteroids and antiallergic or immunomodulating therapies. Inhaled corticosteroids (ICSs) and bronchodilators have been the mainstay. However, in Asia, myths and fallacies regarding Western medicine and corticosteroids are prevalent and lead to nonadherence to treatment. Also, use of traditional and proprietary herbal medicines is popular. In the past decades, a novel class of nonsteroidal immunomodulating montelukasts has become available. This article reviews the evidence for the effectiveness and clinical efficacy of these medications. A number of randomized and controlled trials have been performed over the years. The majority of studies confirm the usefulness of montelukast as monotherapy and add-on therapy to ICS in mild to moderate childhood asthma across all age groups. ICSs are generally superior to montelukasts for asthma management. However, montelukast has a place in the treatment of young children with viral-triggered wheezing diseases, exercise-induced asthma, and in children whose parents are steroid-phobic and find ICS unacceptable.
Topics: Acetates; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Clinical Trials as Topic; Cyclopropanes; Glucocorticoids; Humans; Medication Adherence; Quality of Life; Quinolines; Sulfides
PubMed: 25061277
DOI: 10.2147/DDDT.S39100 -
Medicine Dec 2021Cough variant asthma in children is a special type of asthma. Although there are many effective cases of combined acupuncture and western medicine in the clinical...
BACKGROUND
Cough variant asthma in children is a special type of asthma. Although there are many effective cases of combined acupuncture and western medicine in the clinical treatment of this kind of children, there is no standardized acupuncture combined with western medicine to evaluate the curative effect. Therefore, combined with existing reports, a systematic review and meta-analysis of acupuncture combined with montelukast sodium in the treatment of cough variant asthma in children were carried out to obtain conclusive results.
METHODS
The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and October 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to acupuncture combined with montelukast sodium on cough variant asthma in children were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures.
RESULTS
This study provides a high-quality synthesis to assess the effectiveness and safety of acupuncture combined with montelukast sodium on cough variant asthma in children.
CONCLUSION
This systematic review will provide evidence to determine whether acupuncture combined with montelukast sodium is an effective and safe intervention for patients with cough variant asthma in children.
INPLASY REGISTRATION NUMBER
INPLASY2021110006.
Topics: Acetates; Acupuncture Therapy; Anti-Asthmatic Agents; Asthma; Child; Combined Modality Therapy; Cough; Cyclopropanes; Humans; Meta-Analysis as Topic; Quinolines; Research Design; Sulfides; Systematic Reviews as Topic; Treatment Outcome
PubMed: 34941045
DOI: 10.1097/MD.0000000000028048 -
Medical Science Monitor : International... Mar 2019BACKGROUND Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in preterm infants. Montelukast, an effective cysteinyl leukotriene (cysLT) receptor...
BACKGROUND Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in preterm infants. Montelukast, an effective cysteinyl leukotriene (cysLT) receptor antagonist, has a variety of pharmacological effects and has protective effects against a variety of diseases. Currently, the efficacy and safety of montelukast sodium in treating BPD has been revealed, however, the precise molecular mechanism of the effect of montelukast on BPD development remain largely unclear. Therefore, this study aimed to investigate the effect and mechanism of montelukast on BPD in vivo and in vitro. MATERIAL AND METHODS A mouse BPD model and hyperoxia-induced lung cell injury model were established and treated with montelukast. Then mean linear intercept (MLI), radial alveolar count (RAC), lung weight/body weight (LW/BW) ratio, pro-inflammatory factors, and oxidative stress-related factors in lung tissues were determined. Cell viability and apoptosis were detected using MTT assay and flow cytometer respectively. RESULTS The results showed that montelukast treatment relieved mouse BPD, evidenced by increased RAC and decreased MLI and LW/BW ratios. We also found that montelukast treatment reduced pro-inflammatory factors (TNF-alpha, IL-6, and IL-1ß) production, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) content in the lung tissues of BPD mice. Besides, montelukast eliminated the reduced cell viability and enhanced cell apoptosis induced by hyperoxia exposure in vitro. Moreover, the upregulated pro-inflammatory factors production and p-p65 protein level in lung cells caused by hyperoxia were decreased by montelukast treatment. CONCLUSIONS Montelukast protected against mouse BPD induced by hyperoxia through inhibiting inflammation, oxidative stress, and lung cell apoptosis.
Topics: Acetates; Animals; Animals, Newborn; Apoptosis; Bronchopulmonary Dysplasia; Cyclopropanes; Disease Models, Animal; Hyperoxia; Interleukin-1beta; Interleukin-6; Lung; Lung Injury; Mice; Mice, Inbred C57BL; Oxidative Stress; Quinolines; Receptors, Leukotriene; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 30862773
DOI: 10.12659/MSM.912774 -
Journal of Cardiothoracic Surgery May 2017Lung transplantation is the only effective treatment for end-stage lung diseases. Bronchiolitis obliterans, which is known as non-infectious chronic lung allograft...
BACKGROUND
Lung transplantation is the only effective treatment for end-stage lung diseases. Bronchiolitis obliterans, which is known as non-infectious chronic lung allograft dysfunction (CLAD) in the new classification, is the greatest threat to long-term survival after lung transplantation. This study investigated the role of leukotriene B4 (LTB4) and montelukast in transplantation-related bronchiolitis obliterans and discussed the pathophysiological significance of LTB4 in chronic rejection.
METHODS
Rats were randomly divided into an experimental group (montelukast), a positive control group (dexamethasone), and a blank control group (normal saline solution; NS). Each piece of trachea removed from a F344 rat was transplanted into a Lewis rat through a 5-mm incision at the episternum by subcutaneous embedding. The recipients were treated with gastric lavage with 3 mg/kg · d montelukast suspension, 1 mg/kg · d dexamethasone, and 1 mL/kg · d NS, respectively, in each group. On Day 28, peripheral blood was drawn to measure the white blood cell counts and plasma LTB4 levels. The donor specimens were stained by H-E and Masson, and their organizational structure and extent of fibrosis were visually assessed. The measurement data were compared using one-way analysis of variance, and the categorical data were compared using the chi-square test. A P value of less than 0.05 was considered to indicate statistical significance.
RESULTS
The white blood cell counts of the montelukast, dexamethasone, and NS groups were (16.0 ± 4.2) × 10/L, (19.5 ± 11.6) × 10/L, and (25.8 ± 3.6) × 10/L; no statistical significance was found (P = 0.101). The concentrations of LTB4 were 2230 ± 592 pg/mL, 1961 ± 922 pg/mL, and 3764 ± 1169 pg/mL, and statistical significance was found between the NS group and each of the others (P = 0.009). The percentages of tracheal occlusion were 73.6% ± 13.8%, 23.4% ± 3.2%, and 89.9% ± 11.3%, and statistical significance was found among the three groups (P = 0.000).
CONCLUSIONS
The study established a model to simulate bronchiolitis obliterans after clinical lung transplantation. Oral administration of montelukast reduced plasma LTB4 levels in rats and played a preventive role against tracheal fibrosis after transplantation. This suggests that LTB4 may be involved in bronchiolitis obliterans after pulmonary transplantation. This study indicates a new direction for research into the prevention and treatment of bronchiolitis obliterans after lung transplantation.
Topics: Acetates; Administration, Oral; Animals; Bronchiolitis Obliterans; Cyclopropanes; Disease Models, Animal; Graft Rejection; Leukotriene Antagonists; Leukotriene B4; Lung Transplantation; Male; Quinolines; Rats; Rats, Inbred F344; Rats, Inbred Lew; Sulfides; Transplantation, Homologous
PubMed: 28545478
DOI: 10.1186/s13019-017-0605-5 -
The European Respiratory Journal Jun 2009Montelukast and desloratadine synergistically inhibit the allergen-induced early asthmatic response. Montelukast also suppresses the allergen-induced late asthmatic... (Randomized Controlled Trial)
Randomized Controlled Trial
Montelukast and desloratadine synergistically inhibit the allergen-induced early asthmatic response. Montelukast also suppresses the allergen-induced late asthmatic response, but there are no reports on the effect of desloratadine or the combination on the allergen-induced late asthmatic response. Atopic asthmatics (n = 10) completed a multicentric randomised double-blind crossover study comparing single-dose placebo, 5 mg desloratadine, 10 mg montelukast and the combination administered 2 h prior to allergen inhalation challenge. Methacholine challenges were performed 24 h before and after allergen challenge. Exhaled nitric oxide measurements and sputum inflammatory cell counts were also carried out. All active treatments significantly decreased the late asthmatic response area under the curve. Combination therapy provided the greatest inhibition compared to desloratadine and montelukast. Montelukast was nonsignificantly better than desloratadine but not as effective as the combination. There was a trend towards a decrease in airway responsiveness following montelukast and combination. Montelukast, but not desloratadine or the combination, decreased exhaled NO levels 24 h after allergen. The allergen-induced increase in sputum eosinophil numbers was significantly suppressed at 7 h with desloratadine and combination therapy, and at 24 h with montelukast and combination therapy. Single-dose co-administration of desloratadine and montelukast 2 h prior to allergen inhalation clinically abolished the late asthmatic response and eosinophil recruitment.
Topics: Acetates; Adult; Allergens; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Methacholine Chloride; Middle Aged; Nitric Oxide; Placebos; Quinolines; Respiratory Function Tests; Sputum; Sulfides; Treatment Outcome
PubMed: 19164343
DOI: 10.1183/09031936.00169008 -
Acta Cirurgica Brasileira 2020To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia.
The examination of the nephroprotective effect of montelukast sodium and N-acetylcysteine ın renal ıschemia with dimercaptosuccinic acid imaging in a placebo-controlled rat model.
PURPOSE
To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia.
METHODS
Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups).
RESULTS
On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups.
CONCLUSION
The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.
Topics: Acetates; Acetylcysteine; Animals; Cyclopropanes; Kidney; Quinolines; Rats; Rats, Wistar; Reperfusion Injury; Succimer; Sulfides; Tomography, X-Ray Computed
PubMed: 33084735
DOI: 10.1590/s0102-865020200090000005 -
PloS One 2022Cysteinyl leukotriene receptor 1 (CysLTR1) is a G protein-coupled receptor for the inflammatory lipid mediators cysteinyl leukotrienes, which are involved in smooth...
Cysteinyl leukotriene receptor 1 (CysLTR1) is a G protein-coupled receptor for the inflammatory lipid mediators cysteinyl leukotrienes, which are involved in smooth muscle constriction, vascular permeability, and macrophage chemokine release. The Cysltr1 gene encoding CysLTR1 is expressed in the macrophage lineage, including osteoclasts, and the CysLTR1 antagonist Montelukast has been shown to suppress the formation of osteoclasts. However, it currently remains unclear whether CysLTR1 is involved in osteoclast differentiation and bone loss. Therefore, to clarify the role of CysLTR1 in osteoclastogenesis and pathological bone loss, we herein generated CysLTR1 loss-of-function mutant mice by disrupting the cysltr1 gene using the CRISPR-Cas9 system. These mutant mice had a frameshift mutation resulting in a premature stop codon (Cysltr1 KO) or an in-frame mutation causing the deletion of the first extracellular loop (Cysltr1Δ105). Bone marrow macrophages (BMM) from these mutant mice lost the intracellular flux of calcium in response to leukotriene D4, indicating that these mutants completely lost the activity of CysLTR1 without triggering genetic compensation. However, disruption of the Cysltr1 gene did not suppress the formation of osteoclasts from BMM in vitro. We also demonstrated that the CysLTR1 antagonist Montelukast suppressed the formation of osteoclasts without functional CysLTR1. On the other hand, disruption of the Cysltr1 gene partially suppressed the formation of osteoclasts stimulated by leukotriene D4 and did not inhibit that by glutathione, functioning as a substrate in the synthesis of cysteinyl leukotrienes. Disruption of the Cysltr1 gene did not affect ovariectomy-induced osteoporosis or lipopolysaccharide-induced bone resorption. Collectively, these results suggest that the CysLT-CysLTR1 axis is dispensable for osteoclast differentiation in vitro and pathological bone loss, while the leukotriene D4-CysTR1 axis is sufficient to stimulate osteoclast formation. We concluded that the effects of glutathione and Montelukast on osteoclast formation were independent of CysLTR1.
Topics: Female; Mice; Animals; Osteoclasts; Leukotriene D4; Bone Resorption; Leukotrienes; Glutathione
PubMed: 36395281
DOI: 10.1371/journal.pone.0277307