PMID- 24518411
OWN - NLM
STAT- MEDLINE
DCOM- 20141009
LR  - 20181231
IS  - 1537-4505 (Electronic)
IS  - 1531-7129 (Linking)
VI  - 35
IP  - 3
DP  - 2014 Mar
TI  - Mitochondria-targeted antioxidant MitoQ reduces gentamicin-induced ototoxicity.
PG  - 533-9
LID - 10.1097/MAO.0000000000000192 [doi]
AB  - HYPOTHESIS: Oral supplementation with mitoquinone (MitoQ) prevents 
      gentamicin-induced ototoxicity in guinea pigs. BACKGROUND: 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. METHODS: 
      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. RESULTS: 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). CONCLUSION: 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.
FAU - Ojano-Dirain, Carolyn P
AU  - Ojano-Dirain CP
AD  - Departments of *Otolaryngology - Head and Neck Surgery and daggerSpeech, Language, and 
      Hearing Sciences, University of Florida, Gainesville, Florida, U.S.A.
FAU - Antonelli, Patrick J
AU  - Antonelli PJ
FAU - Le Prell, Colleen G
AU  - Le Prell CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Otol Neurotol
JT  - Otology & neurotology : official publication of the American Otological Society, 
      American Neurotology Society [and] European Academy of Otology and Neurotology
JID - 100961504
RN  - 0 (Antioxidants)
RN  - 0 (Gentamicins)
RN  - 0 (Organophosphorus Compounds)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology/*therapeutic use
MH  - Apoptosis/drug effects/physiology
MH  - Cochlea/*drug effects/metabolism
MH  - Cochlear Diseases/chemically induced/*drug therapy/metabolism
MH  - Evoked Potentials, Auditory, Brain Stem/*drug effects/physiology
MH  - Gentamicins
MH  - Guinea Pigs
MH  - Hearing Loss/chemically induced/*drug therapy/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Organophosphorus Compounds/pharmacology/*therapeutic use
MH  - Oxidation-Reduction
MH  - Oxidative Stress/drug effects/physiology
MH  - Superoxide Dismutase/metabolism
MH  - Ubiquinone/*analogs & derivatives/pharmacology/therapeutic use
EDAT- 2014/02/13 06:00
MHDA- 2014/10/10 06:00
CRDT- 2014/02/13 06:00
PHST- 2014/02/13 06:00 [entrez]
PHST- 2014/02/13 06:00 [pubmed]
PHST- 2014/10/10 06:00 [medline]
AID - 00129492-201403000-00024 [pii]
AID - 10.1097/MAO.0000000000000192 [doi]
PST - ppublish
SO  - Otol Neurotol. 2014 Mar;35(3):533-9. doi: 10.1097/MAO.0000000000000192.