Supplementation With Curcumin Exhibits Nephroprotective Effects in Cisplatin-Induced Acute Kidney Injury

Cisplatin is used as a broad-spectrum chemotherapeutic agent for the treatment of many solid malignancies. With the widespread use of cisplatin, the side effects (especially nephrotoxicity) exhibited are becoming increasingly evident. There are no clinically effective drugs to prevent or treat cisplatin-induced nephrotoxicity. Recently, curcumin has received widespread attention in the field of dietary supplements. In this study, we investigated whether curcumin could attenuate cisplatin-induced renal tubular epithelial cell injury, mitochondrial damage, and reactive oxygen species (ROS) accumulation by in vitro experiments. Subsequently, we evaluated the effects of curcumin supplementation on mitochondrial dynamics, oxidative stress levels, and apoptosis induced by cisplatin. Moreover, renal transporter expression and urinary toxins accumulation were also assessed. Cisplatin-induced nephrotoxicity was caused by dysregulation of mitochondrial homeostasis, leading to excessive oxidative stress and apoptosis in the kidney, as well as dysregulation of renal transporter expression, leading to the accumulation of urinary toxins. However, curcumin could restore mitochondrial homeostasis through the AMPK/PGC-1α/Sirt3 pathway, alleviate renal oxidative stress and apoptosis through the Nrf2/Keap1 and Bax/Bcl2/Caspase-3 pathways, and regulate renal transporter expression to alleviate urinary toxins accumulation, which ultimately alleviated cisplatin-induced nephrotoxicity.