Puerarin alleviates the ototoxicity of gentamicin by inhibiting the mitochondria‑dependent apoptosis pathway.

Abstract

Gentamicin (GM) is a commonly used antibiotic, and ototoxicity is one of its side effects. Puerarin (PU) is an isoflavone in kudzu roots that exerts a number of pharmacological effects, including antioxidative and free radical scavenging effects. The present study investigated whether PU could protect against GM-induced ototoxicity in C57BL/6J mice and House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. C57BL/6J mice and HEI-OC1 cells were used to establish models of GM-induced ototoxicity in this study. Auditory brainstem responses were measured to assess hearing thresholds, and microscopy was used to observe the morphology of cochlear hair cells after fluorescent staining. Cell viability was examined with Cell Counting Kit-8 assays. To evaluate cell apoptosis and reactive oxygen species (ROS) production, TUNEL assays, reverse transcription-quantitative PCR, DCFH-DA staining, JC-1 staining and western blotting were performed. PU protected against GM-induced hearing damage in C57BL/6J mice. PU ameliorated the morphological changes of mouse cochlear hair cells and reduced the apoptosis rate of HEI-OC1 cells after GM-mediated damage. GM-induced ototoxicity may be closely related to the upregulation of p53 expression and the activation of endogenous mitochondrial apoptosis pathways, and PU could protect cochlear hair cells from GM-mediated damage by reducing the production of ROS and inhibiting the mitochondria-dependent apoptosis pathway.