Establishment and Validation of an In Vitro Screening Method for Traditional Chinese Medicine-Induced Nephrotoxicity

Abstract

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 μM.