Ma Zhe, Cao Xuexiao, Guo Xiao, Wang Meng, Ren Xiaoliang, Dong Ranran, Shao Rui, Zhu Yan
The Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Evid Based Complement Alternat Med. 2018 Jun 28;2018:2461915. doi: 10.1155/2018/2461915. eCollection 2018.
Renal injury is among the adverse drug reactions (ADRs) caused by herbal medicine products (HMPs). Traditional Chinese medicines (TCMs) have been practiced for over 2000 years in China and East Asia, and herbs are currently used worldwide for the treatment and prevention of chronic and acute disease. Operetta high content analysis (HCA, PerkinElmer, Waltham, MA, USA), which is an in vitro, sensitive, reproducible, multiparametric screening method, was used to evaluate the cytotoxicity of HMPs in cultures of HEK293 human embryo kidney cells. Cytotoxic results were validated by an animal-based subacute toxicity assay. The renal safety of 18 active pharmaceutical agents from 13 TCM herbs with known nephrotoxic potential was evaluated in HEK293 human embryonic kidney cells. A panel of five parameters, cell viability, nuclear area, nuclear roundness, mitochondrial mass, and mitochondrial membrane potential, was utilized to evaluate drug-induced renal mitochondrial and nuclear injury. HCA can be a useful tool for preclinical screening and postclinical evaluation of HMPs. The nephrotoxicity of diosbulbin B and other HMPs was evident at a concentration as low as 0.01 M.
肾损伤是草药产品（HMPs）引起的药物不良反应（ADRs）之一。中药在中国和东亚已经应用了2000多年，目前草药在全球范围内用于治疗和预防急慢性疾病。Operetta高内涵分析（HCA，美国马萨诸塞州沃尔瑟姆市珀金埃尔默公司）是一种体外、灵敏、可重复的多参数筛选方法，用于评估HMPs对HEK293人胚肾细胞培养物的细胞毒性。细胞毒性结果通过基于动物的亚急性毒性试验进行验证。在HEK293人胚肾细胞中评估了13种具有已知肾毒性潜力的中药中18种活性药物成分的肾脏安全性。利用细胞活力、核面积、核圆度、线粒体质量和线粒体膜电位这五个参数组成的指标体系来评估药物诱导的肾脏线粒体和核损伤。HCA可以成为HMPs临床前筛选和临床后评估的有用工具。薯蓣皂苷元B和其他HMPs在低至0.01 M的浓度下肾毒性就很明显。
