Vitamin E reduces cisplatin ototoxicity.

Abstract

Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Vitamin E, a slow-acting free radical scavenger, has been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E as an otoprotectant. Prospective, randomized controlled trial in the rat model. Wistar rats (weight, 261-386 g) were sedated using 172.4 mg/kg intramuscular ketamine and 3.4 mg/kg xylazine. Baseline auditory brainstem response (ABR) testing was performed in response to clicks and 8-, 16-, and 32-kHz tone bursts. After auditory thresholds were determined, the animals received intraperitoneal drug administration according to one of three group classifications. Group 1 received 4 g/kg vitamin E followed after 30 minutes by 16 mg/kg cisplatin. Group 2 received 6 mL/kg soybean oil followed after 30 minutes by cisplatin. Group 3 received soybean oil followed after 30 minutes by 16 mL/kg saline. After 3 days' follow-up, ABR testing was performed and threshold changes were recorded. Cochleae were removed and processed for scanning electron microscopy after follow-up auditory testing was carried out. Group 2 animals showed marked hearing loss with average threshold shifts of 28.75 +/- 2.3 dB for clicks, 30.0 +/- 1.9 dB at 8 kHz, 21.25 +/- 4.0 dB at 16 kHz, and 45.0 +/- 4.2 dB at 32 kHz. No significant loss was observed in group 3 with shifts of 2 +/- 1.3 dB, 3 +/-3.0 dB, -2.2 +/- 3.1 dB, and -1.1 +/- 4.0 dB for clicks and tone bursts at 8, 16, and 32 kHz, respectively. Significant protection was seen in group 1 animals compared with group 2 animals. In the former group, threshold shifts of 12.5 +/- 3.1 dB for clicks, 7.5 +/- 2.5 dB at 8 kHz, 5.0 +/- 3.3 dB at 16 kHz, and 24.4 +/- 5.6 dB at 32 kHz were observed. These findings were supported by the scanning electron microscope observations that severe outer hair cell destruction occurred in group 2 rats, whereas outer hair cells were preserved to a much greater extent in the cochleae of rats in group 1 that were pretreated with vitamin E. Vitamin E appears to have a protective effect against cisplatin ototoxicity.