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Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells

Dalian Ding1,2, Jianhui Zhang2, Haiyan Jiang1

  • 1Center for Hearing and Deafness, University at Buffalo, 137 Cary Hall, Buffalo, NY, 14214, USA.

Neurotoxicity Research
|January 31, 2020
PubMed

Insights

Ototoxic drugs like gentamicin damage cochlear hair cells, while cisplatin, mefloquine, and cadmium harm support cells first, leading to hearing loss.

Area of Science:

  • Oto-pharmacology
  • Cellular biology
  • Auditory neuroscience

Background:

  • Ototoxic drugs can cause permanent hearing loss by damaging cochlear sensory hair cells.
  • The potential for these drugs to also damage cochlear support cells is largely unexplored.

Purpose of the Study:

  • To investigate the differential effects of ototoxic drugs on cochlear hair cells and support cells.
  • To elucidate the apoptotic pathways involved in drug-induced cochlear cell death.

Main Methods:

  • Postnatal day three rat cochlear cultures were treated with gentamicin, cisplatin, mefloquine, and cadmium.
  • Cell death pathways were analyzed using caspase activation markers.
  • Extracellular matrix component expression (actin, laminin) was quantified.

Main Results:

  • Gentamicin primarily destroyed hair cells via the caspase-9 intrinsic apoptotic pathway.
  • Cisplatin, mefloquine, and cadmium initially damaged support cells (caspase-8 extrinsic pathway) before affecting hair cells.
  • These three drugs reduced actin and laminin, causing sensory epithelium disarray.

Conclusions:

  • Different ototoxic drugs exhibit distinct cellular targets and apoptotic mechanisms within the cochlea.
  • Support cell damage precedes hair cell damage with cisplatin, mefloquine, and cadmium, highlighting their unique toxicity profiles.
  • Disruption of the extracellular matrix by these drugs contributes to cochlear damage and potential hearing loss.
Keywords:
ApoptosisCaspaseCochleaHair cellsNecrosisOtotoxicitySupport cells

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