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P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats     
Yazarlar
Seçkin Özkanlar
Türkiye
Nergis Ulaş
Türkiye
Prof. Dr. Özgür KAYNAR
Kastamonu Üniversitesi, Türkiye
Emine Satıcı
Özet
Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15 mg/kg A-438079. The increase in circulatory IL‐1β and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL‐1β level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats.
Anahtar Kelimeler
Sepsis,Purinergic receptors,Cytokine,Antioxidant,MDA
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Purinergic Signalling
Dergi ISSN 1573-9538
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili Türkçe
Basım Tarihi 03-2023
Cilt No 19
Sayfalar 699 / 707
Doi Numarası 10.1007/s11302-023-09936-z
Makale Linki http://dx.doi.org/10.1007/s11302-023-09936-z