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

• Published in: Hearing research Vol. 198; no. 1; pp. 137 - 143
• Main Authors: Minami, Shujiro B., Sha, Su-Hua, Schacht, Jochen
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2004; Elsevier
• Subjects: Animals; Antineoplastic Agents - adverse effects; Antioxidants - metabolism; Biological and medical sciences; Cisplatin - adverse effects; Cochlea - drug effects; Cochlea - metabolism; Disease Models, Animal; Drug toxicity and drugs side effects treatment; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Evoked Potentials, Auditory, Brain Stem - drug effects; Female; Hair Cells, Auditory - drug effects; Hearing loss; Hearing Loss, Sensorineural - chemically induced; Hearing Loss, Sensorineural - prevention & control; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; Oxidative Stress; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Reactive oxygen species; Reactive Oxygen Species - metabolism; Salicylate; Sodium Salicylate - pharmacology; Sodium Salicylate - therapeutic use; Toxicity: respiratory system, ent, stomatology; Salicylate; Reactive oxygen species; Hearing loss; Animal model; Rat; Toxicity; Brain stem; Central nervous system; Electrophysiology; Auditory disorder; Organ of hearing; Encephalon; ENT disease; Complication; Protection; Internal ear disease; Rodentia; Antioxidant; Cisplatin; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Auditory evoked potential; Ototoxicity
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2004.07.016

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.