Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock

Data de publicação: 01/11/2022

Autores da FMUP

• Marta Fernanda Reina Couto

  Autor

• Janete Maria Quelhas Dos Santos

  Autor

• Maria Paula De Valadares Souto Pinto Serrão

  Autor

• Claudia Camila Rodrigues Pereira Dias

  Autor

• João Tiago De Sousa Pinto Guimarães

  Autor

• Roberto Liberal Fernandes Roncon Albuquerque

  Autor

• José Artur Osório De Carvalho Paiva

  Autor

• Teresa Maria De Jesus Teixeira De Sousa

  Autor

Participantes de fora da FMUP

• Santos-Oliveira, M
• Pereira-Terra, P
• Silva-Pereira, C
• Duarte, A
• Martins, S
• Morato, M.
• Albino-Teixeira, A

Unidades de investigação

• Biomedicina

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• Recursos Comuns

  

  Investigador

  Guilhermina Maria Da Silva Rêgo

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin-angiotensin-aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1-2 (admission), 3-4, and 5-8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-alpha, IL-1 beta, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.

Keywords

• cysteinyl leukotrienes; septic shock; endothelial activation; inflammation; oxidative stress; organ dysfunction