PMID- 22965463
OWN - NLM
STAT- MEDLINE
DCOM- 20130104
LR  - 20181231
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Linking)
VI  - 122
IP  - 11
DP  - 2012 Nov
TI  - Prevention of gentamicin-induced apoptosis with the mitochondria-targeted 
      antioxidant mitoquinone.
PG  - 2543-8
LID - 10.1002/lary.23593 [doi]
AB  - OBJECTIVES/HYPOTHESIS: Antioxidants have been shown to protect against 
      aminoglycoside-induced hearing loss. Mitoquinone (MitoQ) is a 
      mitochondria-targeted derivative of the antioxidant ubiquinone. MitoQ is attached 
      to a lipophilic triphenylphosphonium (TPP) cation, which enables its accumulation 
      inside the mitochondria several hundred-fold over the untargeted antioxidant. The 
      goals of this study were to determine if MitoQ attenuates gentamicin-induced 
      activation of caspase-3/7 activity as a marker of apoptosis and to determine if 
      MitoQ impacts aminoglycoside antimicrobial efficacy. STUDY DESIGN: Prospective 
      and controlled. METHODS: Antibiotic efficacy and minimum inhibitory 
      concentrations (MICs) of gentamicin against three strains each of Staphylococcus 
      aureus, Haemophilus influenzae, and Pseudomonas aeruginosa were evaluated with 
      and without MitoQ using broth dilution methods. Apoptosis was assessed by 
      caspase-3/7 activity in untreated HEI-OC1 cells and cells exposed to 2 mM 
      gentamicin for 24 hours, with and without a 24-hour preincubation with 0.5 muM 
      each of MitoQ, idebenone (an untargeted ubiquinone), or decylTPP (positive 
      control). RESULTS: Gentamicin MICs for P aeruginosa and H influenzae were not 
      affected by MitoQ at pharmacological levels. MICs for S aureus were enhanced by 
      MitoQ. Cell viability was significantly lower in the gentamicin-treated cells. A 
      significant increase in caspase-3/7 activity was observed in cells treated with 
      gentamicin or with idebenone + gentamicin (P = .005). Preincubation with MitoQ 
      decreased the gentamicin-induced apoptosis of HEI-OC1 cells to a greater extent 
      compared to idebenone (P = .002). CONCLUSIONS: MitoQ attenuates 
      gentamicin-induced apoptosis in HEI-OC1 cells and does not compromise gentamicin 
      antibiotic efficacy. MitoQ holds promise as a means of preventing aminoglycoside 
      ototoxicity.
CI  - Copyright (c) 2012 The American Laryngological, Rhinological, and Otological 
      Society, Inc.
FAU - Ojano-Dirain, Carolyn P
AU  - Ojano-Dirain CP
AD  - Department of Otolaryngology, University of Florida College of Medicine, 
      Gainesville, Florida, USA. carolyn.ojano-dirain@ent.ufl.edu
FAU - Antonelli, Patrick J
AU  - Antonelli PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120910
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Gentamicins)
RN  - 0 (Organophosphorus Compounds)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - EC 3.4.22.- (Caspase 3)
RN  - HB6PN45W4J (idebenone)
SB  - IM
MH  - Analysis of Variance
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cell Survival
MH  - Gentamicins/*toxicity
MH  - Haemophilus influenzae/drug effects
MH  - Microbial Sensitivity Tests
MH  - Mitochondria/*drug effects/enzymology
MH  - Organophosphorus Compounds/*pharmacology
MH  - Prospective Studies
MH  - Pseudomonas aeruginosa/drug effects
MH  - Staphylococcus aureus/drug effects
MH  - Ubiquinone/*analogs & derivatives/pharmacology
EDAT- 2012/09/12 06:00
MHDA- 2013/01/05 06:00
CRDT- 2012/09/12 06:00
PHST- 2012/01/12 00:00 [received]
PHST- 2012/05/02 00:00 [revised]
PHST- 2012/06/22 00:00 [accepted]
PHST- 2012/09/12 06:00 [entrez]
PHST- 2012/09/12 06:00 [pubmed]
PHST- 2013/01/05 06:00 [medline]
AID - 10.1002/lary.23593 [doi]
PST - ppublish
SO  - Laryngoscope. 2012 Nov;122(11):2543-8. doi: 10.1002/lary.23593. Epub 2012 Sep 10.