ABSTRACT
Background Ototoxic chemicals can impair the senses of hearing and balance in mammals through irreversible damage to the mechanosensory bundles of inner ear hair cells. Fish and amphibians are useful models for investigating ototoxicity because their inner ear hair cells, like those of mammals, are susceptible to damage by ototoxins. Moreover, amphibian mechanosensation is augmented by a lateral line organ on the body surface that comprises external mechanosensory hair cells. The lateral line hair cells are arranged in clusters (neuromasts) and are structurally and functionally similar to inner ear hair cells, but are more accessible for experimental manipulation. Herein, we implemented neuromasts of the amphibian (Xenopus) lateral line as an organ system for evaluating the effects of ototoxic chemicals, such as antibiotics, on mechanosensory hair cell bundles.
Methods We examined the ultrastructure of larval Xenopus laevis neuromasts with scanning electron microscopy (SEM) after larvae were continuously exposed to ototoxic aminoglycoside antibiotics at sub-lethal concentrations (gentamicin; streptomycin; neomycin) for 72 hours.
Results SEM images demonstrated that 72 hours of exposure to antibiotic concentrations greater than 25 µM reduced the hair cell bundle number in lateral line neuromasts.
Conclusion Therapeutic drug studies will benefit from the incorporation of bioassay strategies that evaluate ototoxicity across multiple species including genera of amphibian origin such as Xenopus. Our outcomes support the use of the Xenopus lateral line for identification of potential ototoxic chemicals and suggest that Xenopus neuromast hair cell bundles can withstand antibiotic exposure. The Xenopus bioassay presented here can be incorporated into drug discovery methodology as a high-resolution phenotypic screen for ototoxic effects.
Summary statement Damage to sensory cells of the inner ear by chemical agents such as antibiotics contributes to the growing global prevalence of disorders of hearing and balance. Our results demonstrate that the Xenopus lateral line, in conjunction with SEM, affords an accessible organ system for otoxicity screens during the drug discovery pipeline.
Competing Interest Statement
The authors have declared no competing interest.
List of Abbreviations
- ESEM
- environmental scanning electron microscopy
- GENT
- gentamicin
- NEO
- neomycin
- SEM
- scanning electron microscopy
- STREP
- streptomycin