Piperazine ferulate attenuates gentamicin-induced acute kidney injury via the NF-κB/NLRP3 pathway

Abstract

BackgroundPiperazine ferulate (PF) is widely used in chronic nephritis and nephrotic syndrome in clinic. PF can improve diseases related inflammation by inhibiting the activation of nuclear factor kappa-B (NF-κB) signal. Acute kidney injury (AKI) is usually associated with the occurrence and development of renal inflammation. However, the nephroprotective effect and anti-inflammatory mechanisms of PF on AKI are not clear. PurposeThis study aimed to investigate the nephroprotective effects of PF on gentamicin (GM) induced AKI in rats and its potential mechanisms. MethodsMale Sprague Dawley (SD) rats were intraperitoneally injected with GM (100 mg/kg/day) with or without PF (50 and 100 mg/kg/day) for 7 consecutive days. In vitro, the NRK-52e cells were exposed to GM (7 mg/ml) with or without PF (62.5 μg/ml) treatment. The renal injury and cell damage were assessed subsequently. ResultsOur findings showed that PF treatment can significantly improve renal function, reduce renal pathological changes, and attenuate inflammatory response in rats treated with gentamicin. Besides, PF could significantly reduce the cell damage and cellular inflammatory response. In terms of mechanisms, our study revealed that PF can evidently inhibit the activation of NF-κB and nod-like receptor family pyrin domain protein 3 (NLRP3) inflammasome. Meanwhile, it could down regulate the expressions of protein and gene of p-IKKα, p-IKKβ, p-p65, p65, p50, p105, NLRP3 and IL-1β. ConclusionOur findings showed that PF may improve inflammation by inhibiting the NF-κB/NLRP3 pathway, so as to attenuate AKI.