Abstract
Graphical abstract demonstrating the role of SIRT1 in the mechanism of protection of kaempferol against doxorubicin (DOX)-induced renal damage. Abbreviations: GSH (glutathione), SOD (superoxide dismutase), ROS (reactive oxygen species), TNF-α (tumor necrosis factor-alpha, IL-6 (interleukin-6), MDA (malondialdehyde).
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•Kaempferol effectively attenuated renal damage and dysfunction in DOX-treated rats.•Mechanisms of protection involve suppressing oxidative stress, inflammation, and apoptosis.•Activation and upregulation of SIRT1 underlie the protection afforded by kaempferol.
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.