OBJECTIVE: Cisplatin is a commonly used chemotherapeutic agent. One of its major dose-limiting side effects is ototoxicity. No treatment has yet been approved for this condition. The objective of this study was to determine the potential protective effect of a systemic administration of erdosteine against cisplatin-induced ototoxicity. STUDY DESIGN: A prospective controlled trial conducted in an animal model. SETTING: Animal care research facilities of The Montreal Children's Hospital Research Institute. SUBJECTS AND METHODS: A total of 27 guinea pigs were assigned to 4 groups, each receiving a different concentration of intraperitoneal erdosteine: group 1 (control group; n = 9) did not receive erdosteine, group 2 (n = 6) received 100 mg/kg/d, group 3 (n = 6) received 200 mg/kg/d, and group 4 (n = 6) received 500 mg/kg/d. The animals in the experimental groups received the erdosteine injection daily for 4 days. All of the animals received 12 mg/kg of intraperitoneal cisplatin. Auditory brainstem response threshold shifts were measured at 4 frequencies (8, 16, 20, and 25 kHz) for all groups. Scanning electron microscopy and outer hair cell counts were performed to assess the protective effect of erdosteine. RESULTS: Significant protection was observed in groups 3 and 4 at 25 kHz. These findings are supported by outer hair cell counts by scanning electron microscopy. CONCLUSION: A systemic administration of erdosteine appears to provide an otoprotective effect at high frequencies for cisplatin-induced ototoxicity.
OBJECTIVE:Cisplatin is a commonly used chemotherapeutic agent. One of its major dose-limiting side effects is ototoxicity. No treatment has yet been approved for this condition. The objective of this study was to determine the potential protective effect of a systemic administration of erdosteine against cisplatin-induced ototoxicity. STUDY DESIGN: A prospective controlled trial conducted in an animal model. SETTING: Animal care research facilities of The Montreal Children's Hospital Research Institute. SUBJECTS AND METHODS: A total of 27 guinea pigs were assigned to 4 groups, each receiving a different concentration of intraperitoneal erdosteine: group 1 (control group; n = 9) did not receive erdosteine, group 2 (n = 6) received 100 mg/kg/d, group 3 (n = 6) received 200 mg/kg/d, and group 4 (n = 6) received 500 mg/kg/d. The animals in the experimental groups received the erdosteine injection daily for 4 days. All of the animals received 12 mg/kg of intraperitoneal cisplatin. Auditory brainstem response threshold shifts were measured at 4 frequencies (8, 16, 20, and 25 kHz) for all groups. Scanning electron microscopy and outer hair cell counts were performed to assess the protective effect of erdosteine. RESULTS: Significant protection was observed in groups 3 and 4 at 25 kHz. These findings are supported by outer hair cell counts by scanning electron microscopy. CONCLUSION: A systemic administration of erdosteine appears to provide an otoprotective effect at high frequencies for cisplatin-induced ototoxicity.