Ecotoxicology and Environmental Safety (Apr 2023)
Ethylbenzene induces hearing loss by triggering mitochondrial impairments and excess apoptosis in cochlear progenitor cells via suppressing the Wnt/β-catenin signaling
Abstract
Ethylbenzene (EB) is widely distributed at low levels in the environment from vehicle emissions, industrial discharge, cigarette smoke, and in some food and consumer products. Evidence shows that EB exposure is associated with hearing loss, yet the mechanisms are unclear. This study aimed to explore the role of the Wnt/β-catenin signaling pathway, which plays a key role during cochlear development, in EB-induced hearing loss. In vitro, we found that EB treatment decreased the viability of cochlear progenitor cells (CPCs), isolated from the cochleae of neonatal rats and crucial for cochlear hair cells generation and hearing construction, via inducing mitochondrial impairments and excessive apoptosis. These were accompanied by the inactivation of the Wnt/β-catenin signaling cascade, as manifested by the decreased levels of related molecules β-catenin, LEF-1 and Lgr5. These findings were further confirmed by knocking down β-catenin and immunofluorescence analysis. Interestingly, adenovirus-mediated β-catenin overexpression activated the Wnt/β-catenin signaling network, alleviated mitochondrial impairments, reduced cell apoptosis, therefore promoting CPCs survival under EB treatment conditions. Finally, using adult Sprague–Dawley rats as an in vivo model with EB inhalation for 13 weeks, we found that exposure to EB decreased body weight gain, increased the hearing thresholds at different exposure stages, along with Wnt/β-catenin signaling pathway suppression in cochlear tissue. More importantly, cochlear microinjection of recombinant lentivirus expressing β-catenin significantly reversed EB-elicited these deleterious effects. Collectively, our results indicate that EB induces hearing loss by triggering mitochondrial impairments and excess apoptosis in CPCs via suppressing the Wnt/β-catenin signaling, and provide clues for the possible therapy.
