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

Abstract

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.

• Authors: Tamer Erdem, Orhan Ozturan, Mustafa Iraz, Murat Cem Miman, Ercument Olmez
• Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (Eur Arch Otorhinolaryngol) Vol. 262 Issue 4 Pg. 314-21 (Apr 2005) ISSN: 0937-4477 [Print] Germany
• PMID: 15170574 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antioxidants
• Amikacin
• Melatonin

Topics

• Amikacin (adverse effects)
• Animals
• Anti-Bacterial Agents (adverse effects)
• Antioxidants (administration & dosage)
• Dose-Response Relationship, Drug
• Hearing Loss (chemically induced, prevention & control)
• Melatonin (administration & dosage)
• Otoacoustic Emissions, Spontaneous (drug effects)
• Rats
• Rats, Sprague-Dawley
• Treatment Outcome