Kaempferol attenuates doxorubicin-mediated nephropathy in rats by activating SIRT1 signaling

Abstract

This study examined if sirtuin-1 (SIRT1) signaling mediates the nephroprotective effect of kaempferol in doxorubicin (DOX)-treated rats. Rats were divided into control, kaempferol, DOX, kaempferol + DOX, and kaempferol + DOX + EX-527 (a SIRT1 inhibitor). Kaempferol preserved the kidney structure and function in DOX-treated rats by attenuating the impairment in urine volume, albumin/creatinine excretion, and creatinine clearance. It also reduced the renal expression of Bax and cleaved caspase-3 and the generation of the reactive oxygen species, malondialdehyde, tumor necrosis factor-α, and interleukin-6 but stimulated levels of glutathione and superoxide dismutase and mRNA of Bcl2. Kaempferol also increased renal mRNA, protein levels, and nuclear activities of SIRT1 that was associated with increased acetylation of both the nuclear factor erythroid 2–related factor 2 (Nrf2) and the nuclear factor-kappa beta (NF-κB). These effects were prevented by co-treatment with EX-527. In conclusion, kaempferol alleviated DOX-induced nephropathy, at least by upregulating and activating SIRT1.