AUTHOR=Mendes Gabriel Moreira de M , Do Nascimento Israel Júnior Borges , Marazzi-Diniz Paulo HS. , Da Silveira Izabela B. , Itaborahy Matheus F. , Viana Luiz E. , Silva Filipe A. , Santana Monique F , Pinto Rebecca AA. , Dutra Bruna G. , Lacerda Marcus Vinicius G. , Araujo Stanley A. , Wanderley David , Vidigal Paula VT. , Diniz Paulo HC , Verano-Braga Thiago , Santos Robson AS. , Leite M Fatima TITLE=The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19 JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1080837 DOI=10.3389/fphys.2022.1080837 ISSN=1664-042X ABSTRACT=

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.