Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model

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Rosa, Ivana F. ; Pecanha, Ana P. B. ; Carvalho, Tabata R. B. ; Alexandre, Leonardo S. ; Ferreira, Vinicius G. ; Doretto, Lucas B. ; Souza, Beatriz M. ; Nakajima, Rafael T. ; da Silva, Patrick ; Barbosa, Ana P. ; Gomes-de-Pontes, Leticia ; Bomfim, Camila G. ; Machado-Santelli, Glaucia M. ; Condino-Neto, Antonio ; Guzzo, Cristiane R. ; Peron, Jean P. S. ; Andrade-Silva, Magaiver ; Camara, Niels O. S. ; Garnique, Anali M. B. ; Medeiros, Renata J. ; Ferraris, Fausto K. ; Barcellos, Leonardo J. G. ; Correia-Junior, Jose D. ; Galindo-Villegas, Jorge ; Machado, Monica F. R. ; Castoldi, Angela ; Oliveira, Susana L. ; Costa, Camila C. ; Belo, Marco A. A. ; Galdino, Giovane ; Sgro, German G. ; Bueno, Natalia F. ; Eto, Silas F. ; Veras, Flavio P. ; Fernandes, Bianca H. V. ; Sanches, Paulo R. S. ; Cilli, Eduardo M. ; Malafaia, Guilherme ; Nobrega, Rafael H. ; Garcez, Aguinaldo S. ; Carrilho, Emanuel ; Charlie-Silva, Ives

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 7, p. 22-pg., 2023-04-01.

Abstract

Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence. (AU)

• FAPESP's process: 20/05761-3 - Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories
• Grantee: Eduardo Maffud Cilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/21739-0 - Antimicrobial activity of proteins secreted by Xanthomonas citri against microorganisms of medical interest
• Grantee: Camila Gasque Bomfim
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/04294-1 - Structural and functional studies of the Xanthomonas citri Type IV Secretion System
• Grantee: Germán Gustavo Sgro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/19939-1 - Effects of marine pharmaceuticals in ZFL cell line
• Grantee: Ives Charlie da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15237-0 - Development of testicular organoids and their use for potential sperm maturation in Zebrafish (Danio rerio) and Tambaqui (Colossoma macropomum)
• Grantee: Ivana Felipe da Rosa
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/07098-0 - Effects of marine pharmaceuticals in zebrafish and ZFL cell line - emphasis
• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/06742-5 - New insights on gonadal signals (growth factors and lncRNAs) that regulate gonadal maturation in fish: basic knowledge and development of biotechnological strategies to delay puberty
• Grantee: Rafael Henrique Nóbrega
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2