PMID- 29194212
OWN - NLM
STAT- MEDLINE
DCOM- 20180622
LR  - 20190107
IS  - 1537-4505 (Electronic)
IS  - 1531-7129 (Print)
IS  - 1531-7129 (Linking)
VI  - 39
IP  - 1
DP  - 2018 Jan
TI  - Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in 
      Guinea Pigs.
PG  - 111-118
LID - 10.1097/MAO.0000000000001638 [doi]
AB  - 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.
FAU - Dirain, Carolyn O
AU  - Dirain CO
AD  - Department of Otolaryngology, University of Florida, Gainesville, Florida.
FAU - Ng, Maria Raye Ann V
AU  - Ng MRAV
FAU - Milne-Davies, Bailey
AU  - Milne-Davies B
FAU - Joseph, Jerin K
AU  - Joseph JK
FAU - Antonelli, Patrick J
AU  - Antonelli PJ
LA  - eng
GR  - R03 DC013659/DC/NIDCD NIH HHS/United States
PT  - Journal Article
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 (Anti-Bacterial Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Organophosphorus Compounds)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - 84319SGC3C (Amikacin)
SB  - IM
MH  - Amikacin/*toxicity
MH  - Animals
MH  - Anti-Bacterial Agents/*toxicity
MH  - Antioxidants/pharmacology
MH  - Evoked Potentials, Auditory, Brain Stem/drug effects
MH  - Guinea Pigs
MH  - Hair Cells, Auditory/drug effects
MH  - Hearing/drug effects
MH  - Hearing Loss/*chemically induced/prevention & control
MH  - Organophosphorus Compounds/*pharmacology
MH  - Otoacoustic Emissions, Spontaneous/drug effects
MH  - Ubiquinone/*analogs & derivatives/pharmacology
PMC - PMC5728173
MID - NIHMS913413
COIS- The authors have no financial conflicts to disclose.
EDAT- 2017/12/02 06:00
MHDA- 2018/06/23 06:00
PMCR- 2019/01/01
CRDT- 2017/12/02 06:00
PHST- 2017/12/02 06:00 [pubmed]
PHST- 2018/06/23 06:00 [medline]
PHST- 2017/12/02 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.1097/MAO.0000000000001638 [doi]
PST - ppublish
SO  - Otol Neurotol. 2018 Jan;39(1):111-118. doi: 10.1097/MAO.0000000000001638.