Hearing Toxicity Induced by Tripterygium Glycosides in Zebrafish

Abstract

Tripterygium glycosides (TG) is isolated from an extensively used traditional Chinese medicine herb tripterygium roots and has been extensively used in the treatment of rheumatoid arthritis, nephrotic syndrome, hyperthyroidism and other diseases due to its anti-inflammatory and immunosuppressive effects. Hearing toxicity has been recently associated with TG use in human patients. In this study, authors assessed hearing toxicity and possible molecular toxic mechanisms of TG in a whole animal model. The maximum non-lethal concentration (MNLC) of TG on the zebrafish was 21 mg/L. TG induced zebrafish hair cell loss in a dose-dependent manner (p<0.001), and the saccular otolith size reduction when treated at MNLC (p<0.01). TG treatment resulted in sound-stimulated zebrafish movement reduction (p<0.001); and the rollover zebrafish percentages were elevated as TG treatment concentrations moved up. Following TG treatment, mRNA levels of the zebrafish hearing organ development genes eya1 and val were remarkably downregulated, and the expression of apoptosis-associated genes bax and caspase3 was significantly enhanced (p<0.05). These findings confirm the hearing toxicity of TG and suggest its toxic mechanisms probably are through suppressing hearing cell development and promoting hearing cell apoptosis. Authors recommend zebrafish assay as a quick and reliable screening test of hearing toxicity for drugs and health products.