ubiquinone and Cochlear-Diseases

Oral supplementation with mitoquinone (MitoQ) prevents gentamicin-induced ototoxicity in guinea pigs.. Antioxidants have been shown to protect against aminoglycoside (AG)-induced ototoxicity. MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, is attached to a lipophilic triphenylphosphonium (TPP) cation, which enables its accumulation inside the mitochondria several hundred-fold over the untargeted antioxidant. MitoQ has improved bioavailability and can reach most tissues and has been used in Parkinson's disease and hepatitis C human trials, which demonstrated that MitoQ can be safely used in humans. Thus, MitoQ is a promising novel therapeutic approach for protecting against AG-induced ototoxicity.. Gentamicin-treated guinea pigs were supplied with water alone (control), decyl-TPP (positive control), or MitoQ-supplemented drinking water. Auditory function was assessed by auditory brainstem response. Cochlear damage was assessed using scanning electron microscopy. Western blotting was performed to evaluate changes in proteins related to apoptosis and oxidative damage in the cochlea.. Threshold shifts at 4 and 8 kHz at 4 and 7 weeks after gentamicin treatment were smaller in animals treated with MitoQ compared with those in the control- and decyl-TPP-treated animals (p < 0.05). Protein carbonyls and levels of the proapoptotic protein Bak were lower (p < 0.05 and p = 0.008, respectively), whereas the level of the antioxidant enzyme manganese superoxide dismutase was higher (p = 0.01) in the cochlea of MitoQ-treated animals. The expression of 3-nitrotyrosine and Hrk were not different between groups (p > 0.05).. Oral supplementation with MitoQ attenuated gentamicin-induced cochlear damage and hearing loss in guinea pigs. MitoQ holds promise as a means for protecting against AG ototoxicity.

Topics: Animals; Antioxidants; Apoptosis; Cochlea; Cochlear Diseases; Evoked Potentials, Auditory, Brain Stem; Gentamicins; Guinea Pigs; Hearing Loss; Mitochondria; Organophosphorus Compounds; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Ubiquinone