ZeTox – Toxicology Services

BY
OUR
PLATFORMS

icon-oto-tox OtoTox – Ototoxicology Services

Drug-induced ototoxicity is provoked by widely-used antibiotics and chemotherapeutics damaging hair cells. Interestingly, fish and mammalian hair cells are damaged by the same chemical and acoustic inputs, including aminoglycosides and platinum derivatives. Zebrafish model organisms have made in vivo testing feasible, not only because of the small quantities of compounds required for the testing but also because of the short lead times for the generation of results.

Figure. Zebrafish neuromasts organization.

Advantages

Zebrafish hair cells have high morphological and physiological homology with mammalian hair cells. 

Zebrafish a perfect model to study ototoxicity compounds.

Hair cells of the zebrafish lateral line are identical to the mammal's inner ear and allow easy assessment of ototoxicity since compounds can be directly added to fish water.

Method description

Transgenic zebrafish larvae expressing the green fluorescent protein in hair cells are exposed to the compound of interest. 120 hours post fecundation, hair cells (HCs) of posterior lateral line neuromasts are imaged and counted. Optionally, larvae can be incubated with another live dye to visualize functional hair cells.

Readouts

Figure: Neuromast hair cell counting of larvae treated with different concentrations of cisplatin  and neomycin compared to negative control DMSO (a). Neuromast images (b)

References

  1. Monroe, J. D., G. Rajadinakaran and M. E. Smith (2015). Sensory hair cell death and regeneration in fishes. Front Cell Neurosci.
  2. Ton, C. and C. Parng (2005). The use of zebrafish for assessing ototoxic and otoprotective agents. Hear Res
  3. Harris, J. A., A. G. Cheng, L. L. Cunningham, G. MacDonald, D. W. Raible and E. W. Rubel 2003. Neomycin-induced hair cell death and rapid regeneration in the lateral line of zebrafish (Danio rerio). J Assoc Res Otolaryngol.