Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Department of Clinical Pharmacology, Second Hospital of Anhui Medical University, Hefei 230601, China.
Molecules. 2022 Dec 5;27(23):8564. doi: 10.3390/molecules27238564.
Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.
庆大霉素（GEN）是一种氨基糖苷类抗生素，具有肾毒性的不良反应。目前，尚无针对肾毒性的有效措施。本研究中，绿茶中的有用成分表没食子儿茶素没食子酸酯（EG）被用来减轻其肾毒性。结果表明，EG 可显著减轻 GEN 注射大鼠的肾损伤以及丙二醛（MDA）的增加和谷胱甘肽（GSH）的减少。在 NRK-52E 细胞中，GEN 在早期治疗阶段增加了细胞内 ROS，并且从 1.5 H 到 24 H 持续保持高 ROS 水平。此外，EG 减轻了 GEN 引起的 ROS 和 MDA 的增加以及 GSH 的减少。此外，EG 激活了核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）的蛋白水平。在用 GEN 处理后，Cleaved-caspase-3 的蛋白水平、流式细胞术分析和 JC-1 染色、谷胱甘肽过氧化物酶 4（GPX4）和 SLC7A11 的蛋白水平均发生了很大变化，表明同时发生了细胞凋亡和铁死亡，而 EG 可以减少这些变化。然而，当用 siRNA 敲低 Nrf2 时，EG 的上述保护作用减弱。综上所述，EG 通过抑制细胞凋亡和铁死亡来减轻 GEN 诱导的肾毒性。
