The protective effect of dexamethasone and lactate against cisplatin-induced ototoxicity

Aim: To compare the protective effect of dexamethasone and lactate against cisplatin-induced ototoxicity. Materials and methods: Thirty Wistar rats were randomly divided into 4 groups. After the rats were sedated with intraperitoneal (IP) ketamine hydrochloride (50 mg/kg) and xylazine (7.5 mg/kg), baseline ABRs (auditory brainstem evoked responses) were measured in response to clicks and tone pips of 4, 8, 12, and 16 kHz. After auditory thresholds were determined, the animals received drug administration as follows: Group 1 (n: 6) received intratympanic (IT) saline (0.9% NaCl) solution, Group 2 (n: 8) IP cisplatin (20 mg/kg) alone, Group 3 (n: 8) IT dexamethasone (0.1-0.3 mL), and Group 4 (n: 8) IT lactated Ringer's (LR) solution (0.1-0.3 mL) followed after 30 min by 20 mg/kg cisplatin. Dexamethasone, LR solution, and saline application were continued for 3 days. At the end of the study, ABR testing was performed and threshold changes were recorded. Results: Group 2 animals showed marked hearing loss with average threshold shifts of 39,6 dB for clicks, 7.2 dB at 4 kHz, 8.4 dB at 8 kHz, 71.1 dB at 12 kHz and 71.8 dB at 16 kHz. No significant loss was observed in Group 3 with average threshold shifts of 1.6 dB, 4.7 dB, 8.7 dB, and 4.2 dB for clicks and tone pips at 4, 8, 12, and 16 kHz, respectively. Similar findings were observed in Group 4 with shifts of 3.5 dB, 6.8 dB, 11.3 dB, and 15.2 dB for clicks and tone pips at 4, 8, 12, and 16 kHz, respectively. Significant protection was seen in Group 3 and 4 animals compared with Group 2 animals. There was no side effect in IT administration of LR solution and dexamethasone for hearing functions. Both of these appear to be easier and safer to apply and have a usable protective effect against cisplatin ototoxicity. Conclusion: IT administration of LR solution and dexamethasone appear to be easy and safe to apply and have a useful protective effect. Clinical applications including these agents could be considered for use in order to reduce the side effects of ototoxic chemotherapy protocols.