Suppression of nF-κB by ro 106-9920 alleviates ischemia/reperfusion-induced renal dysfunction and inflammation via modulation of neutrophil extracellular trap formation in acute kidney injury mice

Neutrophil extracellular trap (NET) formation has been proven to take part in the exacerbation of acute kidney injury (AKI). Ro 106-9920, an effective inhibitor of nuclear factor kappa B (NF-κB) signal, could abrogate the formation of NETs. Herein, we explored whether Ro 106-9920 (Ro) exerts a protective role in AKI by repressing NET formation. The AKI model was induced with 30 min-bilateral renal ischemia followed by reperfusion. After finishing the 7-day treatment of Ro or vehicle, blood and the kidney were collected from each mouse for further analysis. Enzyme-linked immunosorbent assay, H&E, and TUNEL staining, immunohistochemistry, as well as Western blot were carried out to observe the kidney function, renal damage, Apoptosis, and inflammation, and to preliminarily uncover the underlying mechanism. Administration with Ro effectively protected against AKI in a dose-dependent manner, as proven by the reduction of serum creatinine, serum neutrophil gelatinase-associated lipocalin, blood urea nitrogen, and serum inflammatory cytokine in AKI models after its administration. Moreover, Ro significantly alleviated morphological damage, kidney cells Apoptosis, as well as inflammatory cytokine secretion in renal tissues. Mechanically, phosphorylation of NF-κB and myeloperoxidase activity were observed in renal tissues of AKI models, which suggested NF-κB activation and NETosis occurred in AKI. Notably, Ro treatment could significantly repress the nuclear translocation of NF-κB and the increased myeloperoxidase activity. Ro has a protective potential on ischemia/reperfusion-induced AKI by attenuating Apoptosis and inflammation, perhaps by suppressing NF-κB activation and is associated with reduced NETosis.

Acute kidney injury; Ro 106-9920; ischemia/reperfusion injury; neutrophil extracellular trap formation; nuclear factor kappa B.