Effects of melatonin on airway inflammation in experimental models of asthma, COPD and the asthma-COPD overlap
DOI:
https://doi.org/10.11606/issn.1679-9836.v102iespe-204645Keywords:
Melatonin, Inflammation, Remodeling, Asthma, COPD, ACOAbstract
Background and Objectives: According to previous studies, melatonin, an indolamine, may possibly reduce dyspnea in patients with asthma or COPD. Additionally, it has also been proven, through experimental studies, that the molecule possibly plays an anti-inflammatory role, because it might inhibit transcription of NFk-B in experimental models of asthma and COPD. This study aims to investigate the effects of melatonin in experimental models of asthma, COPD and Asthma-COPD Overlap (OCP). Methods: 64 mice were divided into 8 groups in order to induce COPD (group “ALS”), asthma (“OVA”) or OC (“ACO”). The control group (“SAL”) received saline. The treatment groups (“+MEL”) were submitted to both disease protocols and also received Melatonin (intraperitoneally). After the protocols, the exhaled nitric oxide (Eno) and the total and differential cells of the bronchoalveolar lavage fluid were evaluated. Results: OVA+MEL (11.3±1.65ppb) showed reduction in Eno compared to OVA (24.17±4.30ppb). In the analysis of the bronchoalveolar lavage fluid cells, OVA+MEL (11.3±1.65x104 cells/mL) and ACO+MEL (2.17±0.63x104 cells/mL) showed a reduction in the amount of total cells compared to OVA (25.70±4.59x104 cells/mL) and ACO (14.33±3.11x104 cells/mL), respectively. There was a decrease in eosinophil count in OVA+MEL (5.37±1.41x104 cells/mL) and ACO+MEL (0.87±0.36x104 cells/mL) compared to OVA (18.67±4.01x104 cells/mL) and ACO (1.45±0.41x104 cells/mL), respectively. Additionally, the number of lymphocytes decreased in OVA + MEL (1.00±0.24x104 céls./mL) compared to OVA (3.94±1.15x104 cells/mL). The number of macrophages also decreased in OVA + MEL (3.09±0.39x104 cells/mL) and ACO + MEL (1.10±0.27x104 cells/mL) compared to OVA (7.26±1.93x104 cells/mL) and ACO (6.41±1.54x104 cells/mL), respectively. There was no difference in the comparison of neutrophil counts in the different groups analyzed.
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References
Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001;344(5):350-62. doi: 10.1056/NEJM200102013440507
Upparahalli Venkateshaiah S, Manohar M, Kandikattu HK, Mishra A. Experimental Modeling of Eosinophil-Associated Diseases. Methods Mol Biol. 2021;2241:275-291. doi: 10.1007/978-1-0716-1095-4_21
Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000 May;161(5):1720-45. doi: 10.1164/ajrccm.161.5.9903102
GINA. The Global Initiative for Asthma [cited 2021]. Avaliable from: http://www.ginasthma.org.
Global Initiative for Chronic Obstructive Lung Disease - GOLD. 2017. GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD - Global Initiative for Chronic Obstructive Lung Disease - GOLD. Available from: http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/
Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22(4):672-88. doi: 10.1183/09031936.03.00040703
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J, Chakir J. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001;108(3):430-8. doi: 10.1067/mai.2001.117929
Al-Muhsen S, Johnson JR, Hamid Q. Remodeling in asthma. J Allergy Clin Immunol. 2011;128(3):451-62; quiz 463-4. doi: 10.1016/j.jaci.2011.04.047
Viegi G, Pistelli F, Sherrill DL, Maio S, Baldacci S, Carrozzi L. Definition, epidemiology and natural history of COPD. Eur Respir J. 2007;30(5):993-1013. doi: 10.1183/09031936.00082507. PMID: 17978157
Lerner A, Case J, Mori W, et al. Melatonin in peripheral nerve. Nature. 1959;183:1821. https://doi.org/10.1038/1831821a0.
Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol. 2012;351(2):152-66. doi: 10.1016/j.mce.2012.01.004
Pardridge WM, Mietus LJ. Transport of albumin-bound melatonin through the blood-brain barrier. J Neurochem. 1980;34(6):1761-3. doi: 10.1111/j.1471-4159.1980.tb11272.x
Le Bars D, Thivolle P, Vitte PA, Bojkowski C, Chazot G, Arendt J, Frackowiak RS, Claustrat B. PET and plasma pharmacokinetic studies after bolus intravenous administration of [11C] melatonin in humans. Int J Rad Appl Instrum B. 1991;18(3):357-62. doi: 10.1016/0883-2897(91)90132-5
Wang Y, Chen S, Xu S. Effect of melatonin on the expression of nuclear factor-kappa Band airway inflammation in asthmatic rats. Zhonghua Er Ke Za Zhi. 2004;42(2):94-7.
Wang M, LI B, Zhang GH. Melatonin decreases the expression of connective tissue growth factor and inhibite airway remodeling in asthmatic mouse. Basic Clin Med. 2010;3:012.
Campos FL. Estudos do efeito da melatonina sobre a função pulmonar e a qualidade do sono na asma [dissertação]. Fortaleza: Curso de Ciências Farmacêuticas, Universidade Federal do Ceará; 2004.
Aristóteles LRCRB. Anti-IL17 na modulação da mecânica pulmonar, inflamação, estresse oxidativo e remodelamento da matriz extracelular em camundongos com inflamação pulmonar alérgica crônica exarcebada pelo LPS [tese]. São Paulo: , Faculdade de Medicina; 2018 [citado 18 nov. 2022]. doi:10.11606/T.5.2018.tde-31102018-101055
Ikeda G, Miyahara N, Koga H, Fuchimoto Y, Waseda K, Kurimoto E, Taniguchi A, Tanimoto Y, Kataoka M, Tanimoto M, Kanehiro A. Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema. Am J Respir Cell Mol Biol. 2014;50(1):18-29. doi: 10.1165/rcmb.2012-0418OC
Toledo AC, Sakoda CP, Perini A, Pinheiro NM, Magalhães RM, Grecco S, Tibério IF, Câmara NO, Martins MA, Lago JH, Prado CM. Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model. Br J Pharmacol. 2013;168(7):1736-49. doi: 10.1111/bph.12062
Shin N-R, Ko J-W, Kim J-C, et al. Role of melatonin as an SIRT1 enhancer in chronic obstructive pulmonary disease induced by cigarette smoke. J Cell Mol Med. 2020;24:1151–1156. 10.1111/jcmm.14816
Martins-Oliveira BT, Almeida-Reis R, Theodoro-Júnior OA, Oliva LV, Neto dos Santos Nunes N, Olivo CR, Vilela de Brito M, Prado CM, Leick EA, Martins MA, Oliva ML, Righetti RF, Tibério IF. The plant-derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI) attenuates elastase-induced emphysema in mice. Mediators Inflamm. 2016;2016:5346574. doi: 10.1155/2016/5346574
Lemanske RF Jr, Busse WW. Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S95-102. doi: 10.1016/j.jaci.2009.10.047
Rodway GWJ, Choi; Sethi, Hoffman LA, JM. Exhaled nitric oxide in the clinical management of asthma. Curr Allergy Asthma Rep. 2009;4(6):454–459. doi: 10.1007/s11882-004-0011-7
Prado CM, Leick-Maldonado EA, Arata V, Kasahara DI, Martins MA, Tibério IF. Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L741-8. doi: 10.1152/ajplung.00208.2004
Ricciardolo FL, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol Rev. 2004 Jul;84(3):731-65. doi: 10.1152/physrev.00034.2003
Zuo L, Koozechian MS, Chen LL. Characterization of reactive nitrogen species in allergic asthma. Ann Allergy Asthma Immunol. 2014 Jan;112(1):18-22. doi: 10.1016/j.anai.2013.10.007
Habtemariam S, Daglia M, Sureda A, Selamoglu Z, Gulhan MF, Nabavi SM. Melatonin and Respiratory Diseases: A Review. Curr Top Med Chem. 2017;17(4):467-488. doi: 10.2174/1568026616666160824120338
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