Pyrocatechol Alleviates Cisplatin‐Induced Acute Kidney Injury by Inhibiting ROS Production
Xuexia Xie, Fan Wu, Jiaxin Tian, Zhilong Liu, H. He, Dongping Bao, Guoliang Li, Haomin Li, Jianfan Chen, Yiqi Lai, Zheng Chen, Jun Fan, Guo Chen, Caiyong Lai
Abstract
As one of the most common cancer chemotherapy drugs, cisplatin is widely used in cancer management. However, cisplatin‐induced nephrotoxicity occurs in patients who receive this drug. This study is aimed at developing therapeutic agents that effectively alleviate the nephrotoxic effects during cisplatin treatment. We identified a compound named pyrocatechol (PCL) from a natural product library that significantly alleviated cisplatin‐induced cytotoxicity in vitro . Pyrocatechol treatment substantially ameliorated cisplatin (20 mg · kg -1 ) treatment‐induced neuropathological indexes, including inflammatory cell infiltration and apoptosis, in vivo . Mechanistically, pyrocatechol significantly prevented oxidative stress‐induced apoptosis by activating glutathione peroxidase 4 (GPX4) to reduce reactive oxygen species (ROS) accumulation in cisplatin‐treated cells. In addition, pyrocatechol significantly inhibited ROS‐induced JNK/P38 activation. Thus, we found that pyrocatechol prevents ROS‐mediated JNK/P38 MAPK activation, apoptosis, and cytotoxicity through GPX4. Our study demonstrated that pyrocatechol is a novel therapeutic agent against cisplatin‐induced kidney injury.