Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs

Hypothesis: Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. Background: MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. Methods: Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12–18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control). Auditory brainstem responses and distortion product otoacoustic emissions were measured before MitoQ or control solution administration and after amikacin injections. Cochlear hair cell damage was assessed using scanning electron microscopy and Western blotting. Results: With oral administration, animals that received 30 mg/l MitoQ had better hearing than controls at only 24 kHz at 3-week (p = 0.017) and 6-week (p = 0.027) post-amikacin. With subcutaneous administration, MitoQ-injected guinea pigs had better hearing than controls at only 24 kHz, 2-week post-amikacin (p = 0.013). Distortion product otoacoustic emission (DPOAE) amplitudes were decreased after amikacin injections, but were not different between treatments (p > 0.05). Electron microscopy showed minor difference in outer hair cell loss between treatments. Western blotting demonstrated limited attenuation of oxidative stress in the cochlea of MitoQ-supplemented guinea pigs. Conclusions: Oral or subcutaneous MitoQ provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs. Other strategies for attenuating aminoglycoside-induced ototoxicity should be explored. Address correspondence and reprint requests to Carolyn O. Dirain, Ph.D., 1345 Center Dr, M2-228, Gainesville, FL 32610; E-mail: ojanoc@ent.ufl.edu Financial Support: This research was funded by the National Institute on Deafness and Other Communicative Disorder (NIDCD) of the National Institutes of Health (NIH) under award number R03DC013659 to C.O.D. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have no financial conflicts to disclose. Copyright © 2017 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

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