title: Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.
abstract: Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, University of Florida, Gainesville, Florida, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Tate
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, University of Florida, Gainesville, Florida, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Antonelli
authors.affiliation: 2 University of California Los Angeles Medical Center, Los Angeles, California, USA.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Hannabass
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, University of Florida, Gainesville, Florida, USA.
authors.forename: Carolyn O
authors.initials: CO
authors.lastname: Dirain
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D002945:Cisplatin
keywords: cisplatin; guinea pigs; hearing loss; mitoquinone; ototoxicity