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Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024

Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice.

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Lima Erick Bryan de Sousa, Carvalho Antônio Felipe S, Zaidan Isabella, Monteiro Adelson Héric A, Cardoso Camila, Lara Edvaldo S, Carneiro Fernanda S, Oliveira Leonardo C, Resende Filipe, Santos Felipe Rocha da Silva, Souza-Costa Luiz Pedro, Chaves Ian de Meira, Queiroz-Junior Celso M, Russo Remo C, Santos Robson A S, Tavares Luciana P, Teixeira Mauro M, Costa Vivian V, Sousa Lirlândia P

Аннотация

OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice.

METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.

RESULTS: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.

CONCLUSION: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты