Article

Antioxidant protection in a new animal model of cisplatin-induced ototoxicity.

Kresge Hearing Research Institute, University of Michigan, 1301 E. Ann Street, Ann Arbor, MI 48109-0506, USA.
Hearing Research (impact factor: 2.7). 01/2005; 198(1-2):137-43. DOI:10.1016/j.heares.2004.07.016 pp.137-43
Source: PubMed

ABSTRACT Mortality is a major complication in animal models of cisplatin-induced hearing loss due to the systemic toxicity of the drug. Here we report on a novel two-cycle treatment in rats, each cycle consisting of four days of cisplatin injections (1 mg/kg, i.p., twice daily) separated by 10 days of rest. This regimen, similar to clinical courses of cancer chemotherapy, produced significant hearing loss without mortality. Auditory brain stem evoked responses were unchanged after the first cycle but were elevated by 40-50 dB at 16 and 20 kHz after the second. Loss of outer hair cells occurred after the second cycle, predominantly in the base of the cochlea. Total cochlear antioxidants declined progressively during drug treatment and were reduced to 60% of control values after the second cisplatin cycle. Co-administration of salicylate (100 mg/kg, s.c., twice daily) during both cycles or during the second cycle restored antioxidant levels and reduced cisplatin-induced threshold shifts. This model of cisplatin ototoxicity without mortality eliminates potentially confounding factors that may determine the survival of a special cohort of animals. The results also support the notion that reactive oxygen species are involved in cisplatin ototoxicity and show the potential usefulness of antioxidant treatment.

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Keywords

animal models
 
Auditory brain
 
cancer chemotherapy
 
cisplatin injections
 
cisplatin ototoxicity
 
cisplatin-induced hearing loss
 
cisplatin-induced threshold shifts
 
clinical courses
 
drug treatment
 
evoked responses
 
first cycle
 
major complication
 
novel two-cycle treatment
 
outer hair cells
 
potential usefulness
 
reactive oxygen species
 
second cisplatin cycle
 
second cycle
 
significant hearing loss
 
Total cochlear antioxidants
 

Shujiro B Minami