title: Ototoxic interaction between noise and pheomelanin: distortion product otoacoustic emissions after acoustical trauma in chloroquine-treated red, black, and albino guinea pigs.
abstract: This study provides further evidence of an ototoxic interaction between red pheomelanin pigmentation and noise-induced hearing loss. Red, black, and albino guinea pigs were treated with a low, a high, or no dose of chloroquine. The 2f1-f2 distortion product otoacoustic emission (DPOE) measurements were measured before, immediately after, and 1 month after noise exposure to a 1-kHz tone at 105 dB SPL for 72 hours. In red guinea pigs, the DPOE was severely affected by noise trauma when treated even by a low single dose of chloroquine, whereas in both albino and black guinea pigs, the chloroquine effect on the DPOE was temporary and present only when the drug was given in a high single dose. The structure most likely to be responsible for the severe loss of DPOE in chloroquine-treated red animals is the strial melanocyte. The damage may be triggered by an ototoxic noise-induced production of radical oxygen species from pheomelanin, for example, by the Fenton reaction or due to the increased variability of the melanocyte 1 receptor gene as in red-haired individuals.
authors.affiliation: Department of Audiology, Sahlgren's University Hospital, Göteborg, Sweden.
authors.forename: M L
authors.initials: ML
authors.lastname: Barrenäs
authors.forename: K M
authors.initials: KM
authors.lastname: Holgers
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001489:Basilar Membrane / Q000187:drug effects; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008543:Melanins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D013316:Stria Vascularis / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators
chemical_list: D018501:Antirheumatic Agents; D008543:Melanins; D009687:Nuclear Proteins; D015534:Trans-Activators; C018362:pheomelanin; D002738:Chloroquine