Metal-Induced Neuro-Ototoxicity Evidence from Experimental Models

Hearing loss is a major global health burden, and increasing evidence indicates that environmental and occupational exposure to neurotoxic metals may contribute to auditory dysfunction. This narrative review aimed to synthesize experimental evidence on metal-induced neuro-ototoxicity, with particular emphasis on morphological and functional alterations affecting peripheral and central components of the auditory system. A structured literature search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, focusing on animal studies investigating lead, mercury, cadmium, arsenic, and chromium exposure and auditory outcomes. Experimental evidence demonstrates that these metals can induce cochlear hair-cell injury, particularly involving outer hair cells and basal cochlear regions, as well as ribbon synapse loss, spiral ganglion dysfunction, and alterations of the stria vascularis. Central auditory effects include disrupted neural conduction, altered auditory brainstem responses, glial activation, synaptic dysfunction, and changes within the cochlear nucleus and inferior colliculus. Across metals, oxidative and nitrative stress, mitochondrial dysfunction, neuroinflammation, calcium dysregulation, and regulated cell death emerge as interconnected mechanisms. Notably, auditory synaptopathy and central auditory dysfunction may occur with limited overt hair-cell loss. These findings support a multisite model of metal-induced neuro-ototoxicity and highlight the importance of evaluating both peripheral and central auditory pathways in experimental toxicology and environmental health research.