Empagliflozin Alleviates Arsenic Trioxide–Induced Nephrotoxicity by Activating the SIRT1/Akt/Nrf2 Pathway
Chunrong Pang, Wenlei Zhang, Chenli Yue, Haoxuan Li, Jinyan Li, Xinru Wang, Xinsheng Duan, Longyu Li, Zengliang Gao, Xin Hai
TL;DR
Empagliflozin reduces kidney damage caused by arsenic trioxide treatment by activating a protective pathway in the kidneys.
Contribution
This study is the first to show that empagliflozin can alleviate arsenic trioxide-induced nephrotoxicity through the SIRT1/Akt/Nrf2 pathway.
Findings
Empagliflozin improves renal function and reduces kidney structural damage in mice exposed to arsenic trioxide.
Empagliflozin inhibits oxidative stress and apoptosis in HEK293T cells treated with arsenic trioxide.
Empagliflozin activates the SIRT1/Akt/Nrf2 pathway and restores autophagy dysfunction caused by arsenic trioxide.
Abstract
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…
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Taxonomy
TopicsRetinoids in leukemia and cellular processes · Endoplasmic Reticulum Stress and Disease · Chemotherapy-induced organ toxicity mitigation