1. The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19
- Author
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Gabriel Moreira de M Mendes, Israel Júnior Borges Do Nascimento, Paulo HS. Marazzi-Diniz, Izabela B. Da Silveira, Matheus F. Itaborahy, 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, and M Fatima Leite
- Subjects
SARS-cov-2 ,COVID-19 ,hepatic damage ,contact system ,bradykinin ,bradykinin 1 receptor ,Physiology ,QP1-981 - 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.
- Published
- 2022
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