Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model

D. Thomas Dickey, Leslie L. Muldoon, Dale F. Kraemer, Edward A. Neuwelt

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117 Scopus citations


Cisplatin (CDDP) is a widely used chemotherapeutic agent that is highly ototoxic. Animal studies and clinical trials have shown that thiosulfates can protect against platinum-induced ototoxicity. This study investigated a new model for CDDP ototoxicity in the rat, and tested the potential chemoprotective effect of administering N-acetylcysteine (NAC) before giving CDDP. Long Evans rats were treated with CDDP 6 mg/kg delivered to the aorta via a retrograde right external carotid artery infusion, 15 min after intravenous (IV) infusion of saline (n=8) or NAC 400 mg/kg (n=8), such that the vertebral arteries were perfused. Subsequent groups were similarly treated with NAC 30 min before (n=7) and 4 h after (n=7) CDDP. Auditory brainstem response (ABR) thresholds were tested at 4-20 kHz, 7 days after treatment and compared to baseline ABR values. The NAC-treated rats exhibited no significant change from baseline values at all time intervals, while the saline-treated rats showed marked ototoxicity, especially at higher frequencies. Furthermore, the rats treated with NAC 15 min before CDDP exhibited less overall toxicity to CDDP, as evidenced in weight loss 7 days post-treatment (mean for saline=-39.63 g; mean for NAC=-21.13 g; p=0.0084). These data show that treatment with NAC can prevent CDDP-induced ototoxicity in rats.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalHearing Research
Issue number1-2
StatePublished - Jul 2004


  • Animal model
  • Blood-brain barrier
  • Chemoprotection
  • Cisplatin
  • N-Acetylcysteine
  • Ototoxicity

ASJC Scopus subject areas

  • Sensory Systems


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