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


A wide variety of ototoxic drugs are capable of damaging the sensory hair cells in the mammalian cochlea resulting in permanent hearing loss. However, the toxic properties of these drugs suggest that some could potentially damage cochlear support cells as well. To test the hypothesis, we treated postnatal day three rat cochlear cultures with toxic doses of gentamicin, cisplatin, mefloquine, and cadmium. Gentamicin primarily destroyed the hair cells and disrupted the intercellular connection with the surrounding support cells. Gentamicin-induced hair cell death was initiated through the caspase-9 intrinsic apoptotic pathway followed by activation of downstream executioner caspase-3. In contrast, cisplatin, mefloquine, and cadmium initially damaged the support cells and only later damaged the hair cells. Support cell death was initiated through the caspase-8 extrinsic apoptotic pathway followed later by downstream activation of caspase-3. Cisplatin, mefloquine, and cadmium significantly reduced the expression of actin and laminin, in the extracellular matrix, leading to significant disarray of the sensory epithelium.

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Deiters cell


Extracellular matrix




Hensen cells


Inner hair cells


Inner sulcus


Inner sulcus cells




Outer hair cells


Outer sulcus


Pillar cell


Phosphate buffered saline


Support cells


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The research is supported in part by a grant from NIOSH (R01OH010235) and in part by the Foundation of Science and Technology Commission of Shanghai Municipality (#15140900900).

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Correspondence to Richard Salvi.

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Ding, D., Zhang, J., Jiang, H. et al. Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells. Neurotox Res 37, 743–752 (2020).

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  • Hair cells
  • Support cells
  • Cochlea
  • Apoptosis
  • Necrosis
  • Ototoxicity
  • Caspase