title: Post-exposure treatment attenuates noise-induced hearing loss.
abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in sensory cell and neural death in the peripheral nervous system, including damage induced by noise trauma. Antioxidant administration prior to or concomitant with noise exposure can prevent auditory deficits, but the efficacy of a delayed treatment is not known. We have recently found continued reactive oxygen species/reactive nitrogen species formation in the ear for 7-10 days following noise exposure and reasoned that antioxidant intervention during this period should also reduce noise-induced hearing loss. Guinea-pigs were subjected to 4 kHz octave band noise at 120 decibels sound- pressure-level (dB SPL) for 5 hours and received treatment with ROS and RNS scavengers (salicylate and trolox) beginning 3 days prior, 1 hour, 1, 3, or 5 days after noise exposure. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16 kHz, before and 10 days after noise exposure. Hair cell damage was analyzed by quantitative histology, and free radical activity was determined immunohistochemically via 4-hydroxynonenal and nitrotyrosine as markers of reactive oxygen species and reactive nitrogen species action. Delivered up to 3 days after noise exposure, salicylate and trolox significantly reduced auditory brainstem response deficits, reduced hair cell damage, and decreased reactive oxygen species and reactive nitrogen species formation. Earlier drug treatment was more effective than later treatment. Our results detail a window of opportunity for rescue from noise trauma, and provide evidence for both morphological and functional protection by delayed pharmacological intervention.
authors.affiliation: Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yamashita
authors.forename: H-Y
authors.initials: HY
authors.lastname: Jiang
authors.forename: C G
authors.initials: CG
authors.lastname: Le Prell
authors.forename: J
authors.initials: J
authors.lastname: Schacht
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D003051:Cochlea / Q000502:physiology; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced; D007150:Immunohistochemistry; D008297:Male; D017382:Reactive Oxygen Species / Q000378:metabolism; D013016:Sound; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal