Systemic dexamethasone for the prevention of cisplatin-induced ototoxicity

• Published in: European archives of oto-rhino-laryngology 2013-05, Vol.270 (5), p.1597-1605
• Main Authors: Waissbluth, Sofia, Salehi, Pezhman, He, Xinying, Daniel, Sam J.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antineoplastic Agents - adverse effects; Cisplatin - adverse effects; Cochlea - drug effects; Cochlea - pathology; Cochlea - ultrastructure; Dexamethasone - pharmacology; Evoked Potentials, Auditory, Brain Stem - drug effects; Female; Guinea Pigs; Head and Neck Surgery; Hearing Loss, Sensorineural - chemically induced; Hearing Loss, Sensorineural - prevention & control; Medicine; Medicine & Public Health; Microscopy, Electron, Scanning; Neurosurgery; Organ of Corti - drug effects; Organ of Corti - pathology; Organ of Corti - ultrastructure; Otology; Otorhinolaryngology; Prospective Studies; Spiral Ganglion - drug effects; Spiral Ganglion - pathology; Spiral Ganglion - ultrastructure; Spiral Ligament of Cochlea - drug effects; Spiral Ligament of Cochlea - pathology; Spiral Ligament of Cochlea - ultrastructure; Stria Vascularis - drug effects; Stria Vascularis - pathology; Stria Vascularis - ultrastructure; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0937-4477; 1434-4726
• DOI: 10.1007/s00405-012-2150-0

Ototoxicity is a common side effect of cisplatin chemotherapy. This study was undertaken to determine the potential protective effects of a systemic administration of dexamethasone against cisplatin-induced ototoxicity. A prospective controlled trial conducted in an animal model. The setting was Animal care research facilities of the Montreal Children’s Hospital Research Institute. An experimental guinea pig model was used. The animals were divided as follows: group 1 ( n  = 10): 12 mg/kg intraperitoneal (IP) cisplatin, group 2 ( n  = 14): 15 mg/kg/day dexamethasone IP for 2 days followed by cisplatin 12 mg/kg IP, group 3 ( n  = 14): 10 mg/kg/day dexamethasone IP for 2 days, on day 3, they received cisplatin 12 mg/kg IP followed by 20 mg/kg/day dexamethasone for 2 days and group 4 ( n  = 5): 10 ml of saline IP twice a day for 3 days. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (8, 16, 20 and 25 kHz) for groups 1, 2 and 3. Histological changes in the organ of Corti, the stria vascularis, the spiral ligament and the spiral ganglion neurons as well as scanning electron microscopy for outer hair cells were completed. Immunohistochemistry for tumour necrosis factor-alpha (TNF-α) was performed. ABR threshold shifts were similar in all groups. Histological and scanning electron findings demonstrate that dexamethasone has greater protective effect on the stria vascularis. Systemic dexamethasone administration in a guinea pig model did not provide significant protection against cisplatin-induced ototoxicity. Dexamethasone may be useful in future applications as a complementary treatment.