Zebrafish Ototoxicity Assays

Zebrafish Ototoxicity Assays

Hearing loss is one of the most common human sensory disabilities, adversely affecting socialization, communication, mood, physical functioning, and quality of life. Besides age and noise-induced damage, ototoxicity has also become a leading cause of hearing loss, with cisplatin being the prototypical drug associated with chemotherapy-induced hearing loss. Like noise and aging, chemotherapy causes substantial inner ear damage to cochlear hair cells leading to permanent hearing loss for cancer survivors. Most importantly, these hair cells are thought to undergo cell death from noise, ototoxicity, age, and so forth via final common pathways involving oxidative stress and free radical-mediated damage. However, unlike age and noise, ototoxicity is much easier to model experimentally in high-throughput biologically based systems, especially for testing therapeutics. Thus, drug discovery using ototoxicity models to screen compounds may secure results that can then be applied more broadly to treat other causes of hearing loss.

Zebrafish (Danio rerio) has become a widely used model to study disease and in vivo drug development. Zebrafish have neurosensory hair cells on their body surfaces that are aggregated into clumps called neuromasts, which are found at stereotypic positions along their lateral line. These neuromasts and the hair cells contained within them are used to detect changes in movement and vibration from the surrounding water, which mediates schooling, prey capture, and predator avoidance. Hair cells in zebrafish neuromasts are remarkably similar in structure and function to the inner ear hair cells of mammals, making them a good model system. Many drugs that are ototoxic to humans are ototoxic to developing, larval, and adult zebrafish; these include carbonic anhydrase inhibitors, aminoglycoside antibiotics, platinum-based chemotherapies, and environmental metal contaminants. These data suggest that this model is a promising tool to screen novel chemical entities for ototoxicity.

Our Ototoxicity Assay Assessment in Zebrafish

With years of experience and advanced technologies, Creative Biogene has developed in vivo zebrafish assays involving the lateral line for drug ototoxicity screening. Due to their superficial location, zebrafish lateral line hair cells can be experimentally damaged by manipulating conditions in their water (such as adding exogenous toxic agents). We focus on anatomic assays of zebrafish lateral line hair cells, inducing ototoxic damage and utilizing hair cell counts or damage scores to assay rescue by candidate drugs. Moreover, through live imaging and forward genetic screens, we can also provide insight into the chemical and genetic mechanisms of ototoxicity as well as information about whether a protective cotreatment interferes with the therapy.

  • Zebrafish care and breeding
  • Anatomic assay
  • Behavioral assay
  • Video analysis
  • Flow rate experiments
  • Drug exposure experiments
  • Functional recovery experiments
  • Hair cell counts or damage scores

Our Advantages

  • Wide ranges of detection technologies
  • Easy and flexible workflow
  • Advanced high-content screening equipment
  • Excellent predictability

Contact us to learn more about our zebrafish ototoxicity assay services. Our customer service representatives are available 24 hours a day, 7 days a week.

References

  • Todd D W, et al. A fully automated high-throughput zebrafish behavioral ototoxicity assay. Zebrafish, 2017, 14(4): 331-342.
  • Brack C L, Ramcharitar J. Assessment of lateral line function: a potential technique for studies in ototoxicity. Journal of Clinical Neuroscience, 2012, 19(2): 333-335.
  • Niihori M, et al. Zebrafish swimming behavior as a biomarker for ototoxicity-induced hair cell damage: a high-throughput drug development platform targeting hearing loss. Translational Research, 2015, 166(5): 440-450.
  • Cassar S, et al. Use of Zebrafish in Drug Discovery Toxicology. Chemical Research in Toxicology, 2019.

For research use only. Not intended for any clinical use.

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