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Sustainable Development Goals
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- IOC - Artigos de Periódicos [12967]
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INACTIVATED SARS-COV-2 INDUCES ACUTE SKELETAL MUSCLE DAMAGE IN HUMAN K18-HACE2 TRANSGENIC MICE
Brilliant Blue G
Inactivated SARS-CoV-2
Inflammatory mediators
Pannexin-1
Purinergic signaling
Skeletal muscle loss
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Abstract
The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in over 7 million global fatalities and billions of individuals diagnosed with COVID-19. Acute and chronic muscle impairment associated with SARS-CoV-2 infection affected a substantial number of patients, leading to the development of symptoms such as fatigue, muscle pain, and exercise intolerance. Our study introduces an animal model to improve understanding of the pathogenicity caused by SARS-CoV-2 in human skeletal muscle. In this investigation, human angiotensin-converting enzyme 2 under a cytokeratin 18 promoter transgenic mice were subjected to intratracheal instillation with either inactivated SARS-CoV-2 or the virus-free culture medium, with or without pre-treatment with the P2X receptor inhibitor Brilliant Blue G (BBG). Muscle strength, morphology, and inflammatory mediators were measured. Inactivated SARS-CoV-2 induced a significant decrease in mice muscle strength, accompanied by histopathological changes in gastrocnemius and diaphragm muscles, including leukocytic infiltrates, cytoplasmic vacuoles, and centralized nuclei. Also, a notable increase in caspase 3 amount was observed, suggesting muscle apoptosis. Significant elevations were noted in inflammatory mediators in the muscle of inactivated SARS-CoV-2 mice, including high mobility group box-1, tumor necrosis factor-alpha, phospho-nuclear factor kappa B, caspase 11, and pannexin-1. On the other hand, pyroptosis markers such as caspase 1, interleukin-1β, and gasdermin D remained unaltered in all experimental groups. Treatment with BBG mitigated the observed effects, indicating that inhibition of purinergic signaling pathways protects muscles from the inflammatory impact induced by inactivated SARS-CoV-2. This study emphasizes the potential efficacy of purinergic inhibition in ameliorating SARS-CoV-2-induced muscular impairments.
Keywords
ApoptosisBrilliant Blue G
Inactivated SARS-CoV-2
Inflammatory mediators
Pannexin-1
Purinergic signaling
Skeletal muscle loss
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