Nodakenin alleviates renal ischaemia-reperfusion injury via inhibiting reactive oxygen species-induced NLRP3 inflammasome activation.

BACKGROUND

Acute kidney injury (AKI) is a vital contributor to chronic kidney disease and limited therapeutic options are existed to preserve the renal injury. The research presented here investigated the protective effect of nodakenin against AKI and the underlying mechanism.

METHODS

The effect of nodakenin was investigated in ischaemia reperfusion-induced renal injury (IRI) of AKI mice and hypoxia-treated primary renal tubular cells. Briefly, renal functions including creatinine and urea nitrogen were determined and mechanisms associated inflammation were investigated by the advantage of immunohistochemistry, western blot, RT-PCR and flow cytometry.

RESULTS

Deterioration of renal functions including and creatinine, urea nitrogen and tubular necrosis were observed in IRI-AKI model. In contrast, nodakenin strikingly alleviated the deterioration of creatinine, urea nitrogen and tubular necrosis when compared with IRI model. Moreover, nodakenin could significantly inhibit the expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α both in hypoxia-treated primary renal tubular cells and in AKI model. Mechanistic studies revealed that nodakenin dramatically suppressed the production of reactive oxygen species and subsequent NLPR3 inflammasome activation.

CONCLUSION

In summary, these findings provided a solid evidence base and a new drug option for the treatment of AKI.