Aminoguanidine reduces cisplatin ototoxicity

Hear Res. 2003 Dec;186(1-2):10-6. doi: 10.1016/s0378-5955(03)00303-4.

Abstract

Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (*NO) in cisplatin ototoxicity by administering aminoguanidine (AG), a relatively specific inhibitor of inducible nitric oxide synthase (iNOS), in conjunction with cisplatin. Rats were injected with cisplatin, AG, or both. Auditory brainstem evoked responses (ABR) were measured before and 3 days after cisplatin administration. The cochlear tissue was then assayed for *NO and malondialdehyde. Cisplatin alone caused significant ABR threshold shifts at all stimuli tested, whereas AG alone caused no shifts. There was a significant reduction in threshold shift for clicks and 16 kHz tone bursts (but not 32 kHz) when AG was given with cisplatin. The malondialdehyde concentration (but not the *NO concentration) in the AG/cisplatin group was significantly lower than that of the cisplatin group. This suggests that AG reduces cisplatin ototoxicity by directly scavenging hydroxyl radicals. The iNOS pathway may play a role in the generation of free radicals and hearing loss resulting from cisplatin administration, but this conclusion was not supported by our data.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Audiometry, Evoked Response
  • Auditory Threshold / drug effects
  • Cisplatin / toxicity*
  • Enzyme Inhibitors / pharmacology*
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Follow-Up Studies
  • Guanidines / pharmacology*
  • Hearing Loss, High-Frequency / chemically induced
  • Hearing Loss, High-Frequency / prevention & control
  • Hearing Loss, Sensorineural / chemically induced
  • Hearing Loss, Sensorineural / prevention & control
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / analysis
  • Nitric Oxide / analysis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type II
  • Organ of Corti / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Guanidines
  • Nitric Oxide
  • Malondialdehyde
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cisplatin
  • pimagedine