Exposure to ototoxic agents and hearing loss: A review of current knowledge

Several experimental and clinical studies have shown that a variety of ototoxic agents (such as drugs, industrial chemicals and noise) can cause sensorineural hearing loss. The most common ototoxic drugs used in clinical practice include: aminoglycoside and macrolide antibiotics, quinoline anti-malarials, platinum analog antineoplastics, loop diuretics, and acetylsalicylic acid. Among chemical agents with potential ototoxic properties are: organic solvents, heavy metals, organotins, nitriles, asphyxiants, and pesticides/herbicides. Acoustic exposure to high intensity and/or prolonged noise can also cause permanent threshold shifts in auditory perception. Ototoxic agents can infl uence auditory function by different mechanisms: ROS overload, inhibition of mitochondrial protein synthesis, DNA/RNA damage, activation of the apoptotic pathways, excessive calcium infl ux, increase of proinfl ammatory cytokines, interference with fl uid and electrolyte balance of the endolymph, atrophy of the stria vascularis, changes in blood-labyrinth barrier and overstimulation of the stereocilia of the ear cells. Since noise exposure and many drugs or chemical compounds frequently share the same ototoxic mechanisms, this may explain why hearing loss can be potentiated by combined exposure to these agents. However, a great variability in the individual’s response to a given xenobiotic exists and depends on a complex interplay between endogenous and exogenous factors.