Empagliflozin Alleviates Arsenic Trioxide–Induced Nephrotoxicity by Activating the SIRT1/Akt/Nrf2 Pathway

Arsenic trioxide (ATO), utilized in the treatment of acute promyelocytic leukemia (APL), presents significant renal toxicity that restricts its clinical usage. The potential effects of empagliflozin (EMPA) on ATO-induced nephrotoxicity remain unexplored. This study aims to investigate whether EMPA can alleviate ATO-induced nephrotoxicity in both animal and cellular models, as well as to further explore the underlying mechanisms. EMPA can improve renal function in mice and alleviate ATO-induced structural damage to the kidneys. EMPA treatment effectively inhibits ATO-induced oxidative stress and reduces apoptosis. EMPA significantly decreases the production of ROS in cultured HEK293T cells, lowers the apoptotic rate, and safeguards mitochondrial function. EMPA upregulates the SIRT1/Akt/Nrf2 pathway and addresses ATO-induced autophagy dysfunction. These findings suggest that EMPA may ameliorate ATO-induced renal toxicity by activating the SIRT1/Akt/Nrf2 signaling pathway, which is associated with the suppression of oxidative stress, reduction of apoptosis, and protection of mitochondrial functionality.