Dose-dependent dual effect of melatonin on ototoxicity induced by amikacin in adult rats

The aim of this animal study was to reveal the dose-dependent effects of melatonin on aminoglycoside ototoxicity by utilizing distortion product otoacoustic emissions (DPOAEs). Forty-four adult ( aged 12 months) rats were divided into five groups. Rats of the control group ( group C) were injected with vehicle, while the melatonin group ( group M) received melatonin ( 4 mg/kg per day); there were four rats in each of these groups. The study groups consisted of 12 rats per group, and they were treated as follows: 600 mg/kg per day amikacin ( group A), amikacin plus a low dose (0.4 mg/kg per day) melatonin ( group AML) and amikacin plus high dose ( 4 mg/kg per day) melatonin ( group AMH) for 14 days. During the serial measurements on days 0, 5, 10 and 15, the DPOAE results of groups C, M and AML were not significantly changed. Amikacin ototoxicity findings for input/output (I/O) functions were detected on the 3rd measurement of the study in group A. High-dose melatonin clearly enhanced and accelerated amikacin-induced ototoxicity. The DP-gram amplitudes and I/O amplitudes were reduced, and I/O thresholds were increased in group AMH. Group AMH was the group that was affected the most and earliest by amikacin. Our study results showed that while low-dose melatonin protected the inner ear from ototoxicity, high dose melatonin facilitated amikacin-induced ototoxicity, possibly via the vasodilatory effect, leading to an increased accumulation of amikacin in the inner ear. Probably, the protective effect of the melatonin at a dose of 0.4 mg/kg per day is related to its antioxidant properties. Apparently, the vasodilatory effect of melatonin seems to be more prominent than its antioxidant effect in high doses.