P2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis

Purinergic signalling

article

Maria Luciana Larrouyet-Sarto¹  Augusto Shuiti Tamura¹  Vinícius Santos Alves¹  Patrícia T. Santana¹  Roberta Ciarlini-Magalhães¹  Thuany Prado Rangel¹  Cassiana Siebert²  Josiane R. Hartwig²  Tiago Marcon dos Santos²  Angela T.S. Wyse²  Christina Maeda Takiya¹  Robson Coutinho-Silva¹  Luiz Eduardo Baggio Savio¹ 

[1] Instituto de Biofísica Carlos Chagas Filho – Universidade Federal do Rio de Janeiro;Laboratório de Neuroproteção e Doenças Metabólicas, Universidade Federal do Rio Grande do Sul

关键词: Sepsis;    Purinergic signaling;    ATP;    Liver;    Oxidative stress;   

DOI  :  10.1007/s11302-020-09746-7

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY