Open AccessP2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis
Author(s) -
Maria Luciana Larrouyet-Sarto,
Augusto Shuiti Tamura,
Vinícius Santos Alves,
Patrícia Teixeira Santana,
Roberta Ciarlini-Magalhães,
Thuany Prado Rangel,
Cassiana Siebert,
Josiane Rutz Hartwig,
Tiago Marcon dos Santos,
Ângela T. S. Wyse,
Christina Maeda Takiya,
Robson CoutinhoSilva,
Luiz Eduardo Baggio Savio
Publication year - 2020
Publication title -
purinergic signalling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 59
eISSN - 1573-9546
pISSN - 1573-9538
DOI - 10.1007/s11302-020-09746-7
Subject(s) - oxidative stress , tbars , sepsis , inflammation , immunology , liver injury , reactive oxygen species , superoxide dismutase , chemokine , pharmacology , medicine , lipid peroxidation , chemistry , biochemistry
Sepsis is a severe disease characterized by an uncontrolled systemic inflammation and consequent organ dysfunction generated in response to an infection. Extracellular ATP acting through the P2X7 receptor induces the maturation and release of pro-inflammatory cytokines (i.e., IL-1β) and the production of reactive nitrogen and oxygen species that lead to oxidative tissue damage. Here, we investigated the role of the P2X7 receptor in inflammation, oxidative stress, and liver injury in sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in wild-type (WT) and P2X7 knockout (P2X7 -/- ) mice. The oxidative stress in the liver of septic mice was assessed by 2',7'-dichlorofluorescein oxidation reaction (DCF), thiobarbituric acid-reactive substances (TBARS), and nitrite levels dosage. The status of the endogenous defense system was evaluated through catalase (CAT) and superoxide dismutase (SOD) activities. The inflammation was assessed histologically and by determining the expression of inflammatory cytokines and chemokines by RT-qPCR. We observed an increase in the reactive species and lipid peroxidation in the liver of septic WT mice, but not in the liver from P2X7 -/- animals. We found an imbalance SOD/CAT ratio, also only WT septic animals. The number of inflammatory cells and the gene expression of IL-1 β, IL-6, TNF-α, IL-10, CXCL1, and CXCL2 were higher in the liver of WT septic mice in comparison to P2X7 -/- septic animals. In summary, our results suggest that the P2X7 receptor might be a therapeutic target to limit oxidative stress damage and liver injury during sepsis.