Vitamin C alleviates ototoxic effect caused by coadministration of amikacin and furosemide

Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice.

Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD₂₀ and TDD₅₀), respectively. Linear regression analysis was used to determine the TDD₂₀ and TDD₅₀ values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1).

Vitamin C (in a dose of 500 mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD₅₀ values from 49.82 to 21.56 (p <  0.01). In contrast, vitamin C (500 mg/kg, ip) had no significant effect on TDD₂₀ values for the combination of amikacin and furosemide at the fixed-ratio of 1:1.

Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice.