NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
-
Hadi Esmaeili Gouvarchin Ghaleh
Abstract
The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1β in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1β, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1β cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.
Acknowledgments
The authors would like to thank the Clinical Research Development Unit of Baqiyatallah Hospital, Tehran, Iran.
-
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
-
Research funding: None declared.
-
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
-
Ethics approval: The patients participated in the work after obtaining the ethics code approval from the ethics scientific committee (with the ethics number of IR.BMSU.REC.1399.165) as well as the consent form approval.
-
Informed consent: Written informed consent for publication was obtained from each participant.
References
1. Patel, S, Rahmani, B, Gandhi, J, Seyam, O, Joshi, G, Reid, I, et al.. Revisiting the pineal gland: a review of calcification, masses, precocious puberty, and melatonin functions. Int J Neurosci 2020;130:464–75. https://doi.org/10.1080/00207454.2019.1692838.Search in Google Scholar PubMed
2. Tordjman, S, Chokron, S, Delorme, R, Charrier, A, Bellissant, E, Jaafari, N, et al.. Melatonin: pharmacology, functions and therapeutic benefits. Curr Neuropharmacol 2017;15:434–43. https://doi.org/10.2174/1570159x14666161228122115.Search in Google Scholar PubMed PubMed Central
3. Bahrampour Juybari, K, Pourhanifeh, MH, Hosseinzadeh, A, Hemati, K, Mehrzadi, S. Melatonin potentials against viral infections including COVID-19: current evidence and new findings. Virus Res 2020;287:198108. https://doi.org/10.1016/j.virusres.2020.198108.Search in Google Scholar PubMed PubMed Central
4. Fang, Y, Zhao, C, Xiang, H, Zhao, X, Zhong, R. Melatonin inhibits formation of mitochondrial permeability transition pores and improves oxidative phosphorylation of frozen-thawed ram sperm. Front Endocrinol 2019;10:896. https://doi.org/10.3389/fendo.2019.00896.Search in Google Scholar PubMed PubMed Central
5. Sun, H, Gusdon, AM, Qu, S. Effects of melatonin on cardiovascular diseases: progress in the past year. Curr Opin Lipidol 2016;27:408–13. https://doi.org/10.1097/mol.0000000000000314.Search in Google Scholar PubMed PubMed Central
6. Owens, JA. Update in pediatric sleep medicine. Curr Opin Pulm Med 2011;17:425–30. https://doi.org/10.1097/mcp.0b013e32834ba901.Search in Google Scholar
7. Bruinen de Bruin, Y, Lequarre, AS, McCourt, J, Clevestig, P, Pigazzani, F, Zare Jeddi, M, et al.. Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic. Saf Sci 2020;128:104773. https://doi.org/10.1016/j.ssci.2020.104773.Search in Google Scholar PubMed PubMed Central
8. Pietschmann, IS, Mertz, M. Medical humanism and complementary, alternative and integrative medicine. Arch Philos 2020;83:83–102. https://doi.org/10.3917/aphi.834.0083.Search in Google Scholar
9. Choudhry, N, Zhao, X, Xu, D, Zanin, M, Chen, W, Yang, Z, et al.. Chinese therapeutic strategy for fighting COVID-19 and potential small-molecule inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). J Med Chem 2020;63:13205–27. https://doi.org/10.1021/acs.jmedchem.0c00626.Search in Google Scholar PubMed PubMed Central
10. Akbariqomi, M, Hosseini, MS, Rashidiani, J, Sedighian, H, Biganeh, H, Heidari, R, et al.. Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: a single-center, retrospective study in Iran. Diabetes Res Clin Pract 2020;169:108467. https://doi.org/10.1016/j.diabres.2020.108467.Search in Google Scholar PubMed PubMed Central
11. Al Naggar, Y, Giesy, JP, Abdel-Daim, MM, Javed Ansari, M, Al-Kahtani, SN, Yahya, G. Fighting against the second wave of COVID-19: can honeybee products help protect against the pandemic? Saudi J Biol Sci 2021;28:1519–27. https://doi.org/10.1016/j.sjbs.2020.12.031.Search in Google Scholar PubMed PubMed Central
12. Abd Elkodous, M, El-Sayyad, GS, Abdel-Daim, MM. Engineered nanomaterials as fighters against SARS-CoV-2: the way to control and treat pandemics. Environ Sci Pollut Res Int 2020:1–7. https://doi.org/10.1007/s11356-020-11032-3.Search in Google Scholar PubMed PubMed Central
13. Kabir, MT, Uddin, MS, Hossain, MF, Abdulhakim, JA, Alam, MA, Ashraf, GM, et al.. COVID-19 pandemic: from molecular pathogenesis to potential investigational therapeutics. Front Cell Dev Biol 2020;8:616. https://doi.org/10.3389/fcell.2020.00616.Search in Google Scholar PubMed PubMed Central
14. Hasana, S, Hossain, MF, Jalouli, M, Kabir, MT, Uddin, MG, Wahed, MII, et al.. Genetic diversity of SARS-CoV2 and environmental settings: possible association with neurological disorders. Mol Neurobiol 2021;58:1917–31. https://doi.org/10.1007/s12035-020-02239-z.Search in Google Scholar PubMed PubMed Central
15. Lin, H, Cao, X. Nuclear innate sensors for nucleic acids in immunity and inflammation. Immunol Rev 2020;297:162–73. https://doi.org/10.1111/imr.12893.Search in Google Scholar PubMed
16. Lee, S, Channappanavar, R, Kanneganti, TD. Coronaviruses: innate immunity, inflammasome activation, inflammatory cell death, and cytokines. Trends Immunol 2020;41:1083–99. https://doi.org/10.1016/j.it.2020.10.005.Search in Google Scholar PubMed PubMed Central
17. Alon, R, Sportiello, M, Kozlovski, S, Kumar, A, Reilly, EC, Zarbock, A, et al.. Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19. Nat Rev Immunol 2021;21:49–64. https://doi.org/10.1038/s41577-020-00470-2.Search in Google Scholar PubMed PubMed Central
18. Land, WG. DAMP-promoted efferent innate immune responses in human diseases: inflammation. In: Land, WG, editor Damage-associated molecular patterns in human diseases: volume 2: danger signals as diagnostics, prognostics, and therapeutic targets. Cham: Springer International Publishing; 2020:151–209 pp.10.1007/978-3-030-53868-2_5Search in Google Scholar
19. Vural, EM, van Munster, BC, de Rooij, SE. Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature. Drugs Aging 2014;31:441–51. https://doi.org/10.1007/s40266-014-0178-0.Search in Google Scholar PubMed
20. Perez-Garmendia, R, Lopez de Eguileta Rodriguez, A, Ramos-Martinez, I, Zuñiga, NM, Gonzalez-Salinas, R, Quiroz-Mercado, H, et al.. Interplay between oxidative stress, inflammation, and amyloidosis in the anterior segment of the eye; its pathological implications. Oxid Med Cell Longev 2020;2020:6286105. https://doi.org/10.1155/2020/6286105.Search in Google Scholar PubMed PubMed Central
21. Amaral, EP, Vinhaes, CL, Oliveira-de-Souza, D, Nogueira, B, Akrami, KM, Andrade, BB. The interplay between systemic inflammation, oxidative stress, and tissue remodeling in tuberculosis. Antioxidants Redox Signal 2021;34:471–85. https://doi.org/10.1089/ars.2020.8124.Search in Google Scholar PubMed PubMed Central
22. Beltrán-García, J, Osca-Verdegal, R, Pallardó, FV, Ferreres, J, Rodríguez, M, Mulet, S, et al.. Oxidative stress and inflammation in COVID-19-associated sepsis: the potential role of anti-oxidant therapy in avoiding disease progression. Antioxidants 2020;9. https://doi.org/10.3390/antiox9100936.Search in Google Scholar PubMed PubMed Central
23. Arjunan, P. Eye on the enigmatic link: dysbiotic oral pathogens in ocular diseases; the flip side. Int Rev Immunol 2020:1–24. https://doi.org/10.1080/08830185.2020.1845330.Search in Google Scholar PubMed
24. Yu, GM, Kubota, H, Okita, M, Maeda, T. The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells. PLoS One 2017;12:e0178525. https://doi.org/10.1371/journal.pone.0178525.Search in Google Scholar PubMed PubMed Central
25. Huang, SH, Cao, XJ, Wei, W. Melatonin decreases TLR3-mediated inflammatory factor expression via inhibition of NF-kappa B activation in respiratory syncytial virus-infected RAW264.7 macrophages. J Pineal Res 2008;45:93–100. https://doi.org/10.1111/j.1600-079x.2008.00560.x.Search in Google Scholar PubMed
26. Huang, SH, Cao, XJ, Liu, W, Shi, XY, Wei, W. Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J Pineal Res 2010;48:109–16. https://doi.org/10.1111/j.1600-079x.2009.00733.x.Search in Google Scholar
27. Ueda, K, Park, JH, Ochiai, K, Itakura, C. Disseminated intravascular coagulation (DIC) in rabbit haemorrhagic disease. Jpn J Vet Res 1992;40:133–41.Search in Google Scholar
28. Verdonschot, J, Hazebroek, M, Merken, J, Debing, Y, Dennert, R, Brunner-La Rocca, HP, et al.. Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature. Eur J Heart Fail 2016;18:1430–41. https://doi.org/10.1002/ejhf.665.Search in Google Scholar PubMed
29. Ouyang, H, Zhong, J, Lu, J, Zhong, Y, Hu, Y, Tan, Y. Inhibitory effect of melatonin on Mst1 ameliorates myocarditis through attenuating ER stress and mitochondrial dysfunction. J Mol Histol 2019;50:405–15. https://doi.org/10.1007/s10735-019-09836-w.Search in Google Scholar PubMed
30. Zhang, Y, Li, X, Grailer, JJ, Wang, N, Wang, M, Yao, J, et al.. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. J Pineal Res 2016;60:405–14. https://doi.org/10.1111/jpi.12322.Search in Google Scholar PubMed
31. Favero, G, Franceschetti, L, Bonomini, F, Rodella, LF, Rezzani, R. Melatonin as an anti-inflammatory agent modulating inflammasome activation. Internet J Endocrinol 2017;2017:1835195. https://doi.org/10.1155/2017/1835195.Search in Google Scholar PubMed PubMed Central
32. Liu, Z, Gan, L, Xu, Y, Luo, D, Ren, Q, Wu, S, et al.. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue. J Pineal Res 2017;63. https://doi.org/10.1111/jpi.12414.Search in Google Scholar PubMed
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Research Articles
- Isolation and characterization of chemical constituents from Chaerophyllum bulbosum roots and their enzyme inhibitory and antioxidant effects
- Monascin and monascinol, azaphilonoid pigments from Mortierella polycephala AM1: in silico and in vitro targeting of the angiogenic VEGFR2 kinase
- Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies
- NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
- Oxidative stress and cyto-genotoxicity induced by poly-d-glucosamine in human blood cells in vitro
- A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability
- Review Articles
- Cytokine storm syndrome in SARS-CoV-2: a review
- A comprehensive review on the development of probiotic supplemented confectioneries
Articles in the same Issue
- Frontmatter
- Research Articles
- Isolation and characterization of chemical constituents from Chaerophyllum bulbosum roots and their enzyme inhibitory and antioxidant effects
- Monascin and monascinol, azaphilonoid pigments from Mortierella polycephala AM1: in silico and in vitro targeting of the angiogenic VEGFR2 kinase
- Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies
- NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
- Oxidative stress and cyto-genotoxicity induced by poly-d-glucosamine in human blood cells in vitro
- A synergy interaction of artocarpin and tetracycline against Pseudomonas aeruginosa and its mechanism of action on membrane permeability
- Review Articles
- Cytokine storm syndrome in SARS-CoV-2: a review
- A comprehensive review on the development of probiotic supplemented confectioneries