Frontiers in Physiology (Dec 2022)

The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19

  • Gabriel Moreira de M Mendes,
  • Gabriel Moreira de M Mendes,
  • Israel Júnior Borges Do Nascimento,
  • Israel Júnior Borges Do Nascimento,
  • Paulo HS. Marazzi-Diniz,
  • Izabela B. Da Silveira,
  • Izabela B. Da Silveira,
  • Matheus F. Itaborahy,
  • Matheus F. Itaborahy,
  • Luiz E. Viana,
  • Luiz E. Viana,
  • Filipe A. Silva,
  • Monique F Santana,
  • Rebecca AA. Pinto,
  • Bruna G. Dutra,
  • Marcus Vinicius G. Lacerda,
  • Stanley A. Araujo,
  • David Wanderley,
  • Paula VT. Vidigal,
  • Paulo HC Diniz,
  • Thiago Verano-Braga,
  • Robson AS. Santos,
  • M Fatima Leite

DOI
https://doi.org/10.3389/fphys.2022.1080837
Journal volume & issue
Vol. 13

Abstract

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Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.

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