@article{Zhang2023, 
author = {Yunjing Zhang and Jicheng Wu and Quanlin An and Huanhuan Zhu and Xinwan Su and Ying Wang and Xishao Xie and Jian Zhang and Xi Yao and Chunhua Weng and Shi Feng and Jianhua Mao and Xianghui Fu and Fei Han and Xin Cao and Ben Wang and Weiqiang Lin},
title = {Renal tubule-targeted dexrazoxane suppresses ferroptosis in acute kidney injury by inhibiting ACMSD},
year = {2023},
journal = {Nano Research},
volume = {16},
number = {7},
pages = {9701-9714},
keywords = {dexrazoxane, dexrazoxane-polysialic acid, acute kidney injury, ischemia-reperfusion injury, ferroptosis, α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD)},
url = {https://www.sciopen.com/article/10.1007/s12274-023-5547-8},
doi = {10.1007/s12274-023-5547-8},
abstract = {Acute kidney injury (AKI) is a heterogeneous clinical complication with no existing definite or particular therapies. Therefore, molecular mechanisms and approaches for treating acute kidney injury are in urgent need. Herein, we demonstrated that dexrazoxane (DXZ), a U.S. Food and Drug Administration (FDA)-approved cardioprotective drug, can both functionally and histologically attenuate cisplatin or ischemia-reperfusion injury-induced AKI in vitro and in vivo via inhibiting ferroptosis specifically. This effect is characterized by decreasing lipid peroxidation, shown by the biomarker of oxidative stress 4-hydroxynonenal (HNE) and prostaglandinendoperoxide synthase 2 (Ptgs2), while reversing the downregulation of glutathione peroxidase 4 (GPX4) and ferritin 1 (FTH-1). Mechanistically, the results revealed that DXZ targeted at the renal tubule significantly inhibits ferroptosis by suppressing α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD). Furthermore, the conjugation of dexrazoxane and polysialic acid (DXZ-PSA) is specifically designed and utilized to enhance the therapeutic effect of DXZ by long-term effect in the kidney, especially retention and targeting in the renal tubules. This study provides a novel therapeutic approach and mechanistic insight for AKI by inhibiting ferroptosis through a new type drug DXZ-PSA with the enhanced renal distribution.}
}