biostudies-literatureRosa IFSão Paulo Research FoundationBrazilian National Council for Scientific and Technological DevelopmentSão Paulo Research Foundation (FAPESP)CAPES6104https://www.ebi.ac.uk/biostudies/studies/S-EPMC10094635biostudies-literatureUnknown24(7)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 <i>Danio rerio</i> proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (<i>il1b</i>, <i>il6</i>, <i>tnfa</i>, and <i>nfkbiab</i>), oxidative stress (<i>romo1</i>) and energy metabolism (<i>slc2a1a and coa1</i>) 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.International journal of molecular sciencesPhotobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model.PMC1009463588887.504531/2020-00465389/2014-70459/20307743/2018-7Project CG 19,110426531/2018-32020/15237-0303263/2018-02019/21739-02019/19939-12018/07098-020/15237-02014/04294-121/06742-5Bueno NFCastoldi AGuzzo CRBomfim CGPeron JPSSgro GGMedeiros RJCilli EMCarrilho Eda Silva PGaldino GFernandes BHVRosa IFVeras FPAndrade-Silva MNobrega RHPecanha APBMachado-Santelli GMCamara NOSBarcellos LJGCosta CCCarvalho TRBAlexandre LSEto SFFerreira VGFerraris FKBelo MAASouza BMGarnique AMBCondino-Neto ABarbosa APDoretto LBMalafaia GMachado MFRGarcez ASNakajima RTGalindo-Villegas JOliveira SLCorreia-Junior JDCharlie-Silva IGomes-de-Pontes LSanches PRSfalsePhotobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model.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 <i>Danio rerio</i> proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (<i>il1b</i>, <i>il6</i>, <i>tnfa</i>, and <i>nfkbiab</i>), oxidative stress (<i>romo1</i>) and energy metabolism (<i>slc2a1a and coa1</i>) 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.2023-01-01T00:00:00Z2023 Mar2026-06-25T03:09:33.266Z2025-04-05T19:41:36.652ZS-EPMC100946353704707810.3390/ijms24076104