P2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis
| Autor: | Roberta Ciarlini-Magalhães, Tiago Marcon dos Santos, Angela T. S. Wyse, Christina Maeda Takiya, Maria Luciana Larrouyet-Sarto, Luiz Eduardo Baggio Savio, Cassiana Siebert, Thuany Prado Rangel, Augusto Shuiti Tamura, Robson Coutinho-Silva, Vinícius Santos Alves, Josiane R. Hartwig, Patricia T. Santana |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Purinergic P2X Receptor Antagonists Inflammation Systemic inflammation medicine.disease_cause Proinflammatory cytokine Lipid peroxidation Sepsis Superoxide dismutase Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine medicine Humans Animals Molecular Biology Mice Knockout Liver injury biology Liver Diseases Cell Biology medicine.disease Mice Inbred C57BL Oxidative Stress Highlights Endocrinology chemistry biology.protein Original Article Receptors Purinergic P2X7 medicine.symptom Oxidative stress |
| Zdroj: | Purinergic Signal |
| ISSN: | 1573-9546 1573-9538 |
| DOI: | 10.1007/s11302-020-09746-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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