Pharmacological elucidation of the cellular and molecular mechanisms in drug-induced nephrotoxicity and the prevention.

抗mrsa药物万古霉素（VCM）在培养的肾小管LLC-PK1细胞中引起线粒体介导的活性氧（ROS）产生，导致浓度和时间依赖性细胞凋亡。亲脂抗氧化剂维生素E和线粒体靶向抗氧化剂mitoTEMPO可显著阻止vcm诱导的线粒体功能障碍和凋亡。VCM也引起JNK的磷酸化，而JNK抑制剂SP600125对VCM诱导的细胞损伤有显著的抑制作用。

Anti-MRSA drug vancomycin (VCM) caused the mitochondrial-mediated reactive oxygen species (ROS) generation leading to a concentration- and time-dependent cell apoptosis in cultured renal tubular LLC-PK1 cells. A lipophilic antioxidant vitamin E and a mitochondria-targeted antioxidant mitoTEMPO significantly prevented the VCM-induced mitochondrial dysfunction and apoptosis. VCM also caused phosphorylation of JNK, while a JNK inhibitor SP600125 showed a significant suppression against the VCM-induced cell injury.