Renal protection of rhein against 5/6 nephrectomied-induced chronic kidney disease: role of SIRT3-FOXO3 alpha signalling pathway

Objectives The purpose of this study is to investigate the antifibrosis and anti-oxidation of rhein in vivo and in vitro, and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD). Methods In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathologic tests were performed by HE and Masson trichrome stained. The level of ROS was investigated by fluorescence microplate with the probe 2 ', 7 '-dichlorofluorescein diacetate (DCFH-DA). The protein expressions of p47phox and gp91phox were measured in 5/6Nx rats. In HK-2 cells, the expression of SIRT3 and Foxo3 alpha was measured in SIRT3 knockdown conditions. The indicators of oxidation and fibrosisi were measured in SIRT3 knockdown conditions. Key findings The results showed that, in addition to reducing renal interstitial pathologic injury and collagen fibrils, rhein administration improved renal function. The protective mechanisms were attributed to active SIRT3/FOXO3 alpha signalling pathway and then play the anti-oxidative capacity of rhein, as well as to subsequent antifibrotic effect. Conclusion Taken together, rhein protected kidney through SIRT3/FOXO3a involvement. The anti-oxidative capacity of rhein contributed to the protective effects including the subsequent antifibrotic responses.