Cobalt is widely used in the medical industry, mainly including cobalt alloy joint implants and cobalt-chromium porcelain crowns. However, unexplained ototoxicity and neurotoxicity often occur in the clinical use of cobalt agents at present, which limits the development of the cobalt industry. In this study, based on the clinical problem of cobalt ototoxicity, we first conducted an extensive search and collation of related theories, and on this basis, prepared an HEI-OC1 cell model and basilar membrane organotypic cultures after cobalt treatment. We used immunofluorescence staining, western blot, CCK8, and si-RNA to investigate the mechanism of cobalt ototoxicity, to discover its potential therapeutic targets. After comparing the reactive oxygen species, mitochondrial transmembrane potential, apoptosis-related protein expression, and cell viability of different treatment groups, the following conclusions were drawn: cobalt causes oxidative stress in the inner ear, which leads to apoptosis of inner ear cells; inhibition of oxidative stress and apoptosis can alleviate the damage of cobalt on inner ear cells; and the Dicer protein plays a role in the mechanism of inner ear damage and is a potential target for the treatment of cobalt-induced inner ear damage. Taken together, these results suggest that cobalt-induced ototoxicity triggered by oxidative stress activates a cascade of apoptotic events where cCaspase-3 decreases Dicer levels and amplifies this apoptotic pathway. It may be possible to prevent and treat cobalt ototoxicity by targeting this mechanism.
Keywords: Cobalt; Cochlea; Dicer; Hair cells; Spiral ganglion neurons.
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