The ototoxic mechanism of cisplatin.
The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.
McAlpine
D
D
Department of Physiology, University of Western Australia, Nedlands.
Johnstone
B M
BM
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003051:Cochlea / Q000502:physiology; D003055:Cochlear Microphonic Potentials; D004056:Differential Threshold; D004357:Drug Synergism; D004423:Ear / Q000294:innervation / Q000502:physiology*; D004594:Electrophysiology; D005665:Furosemide / Q000494:pharmacology; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced*; D007478:Iontophoresis; D009420:Nervous System / Q000187:drug effects; D010477:Perfusion; D012533:Scala Tympani / Q000187:drug effects
D000625:Aminooxyacetic Acid; D005665:Furosemide; D002945:Cisplatin