Delayed production of free radicals following noise exposure.
Reactive oxygen and reactive nitrogen species (ROS, RNS) formed in the inner ear in response to high-intensity noise are thought to play an important role in noise-induced hearing loss (NIHL). ROS appear rapidly and transiently in the inner ear during and following noise exposure, while hair cell loss progresses over time stabilizing two or more weeks after insult. Although the delayed loss may, in part, reflect slowly progressing apoptotic or necrosis pathways, an alternate hypothesis is that a continued formation of free radicals contributes to cell death. To evaluate this hypothesis, we measured auditory brain stem responses (ABRs), hair cell loss, and free radical activity in the guinea pig following noise exposure (5 h, 120 dB SPL, 1 OCB). Nitrotyrosine (NT) and 4-hydroxy-2-noneal (4-HNE) were used as histochemical markers of RNS and ROS formation, respectively. Assessments were performed prior to and on Days 1, 3, 7, 10, 14 and 21 after exposure. Immunoreactivity to NT and 4-HNE was low initially, reached a maximum at 7 to 10 days, and then declined. ABR thresholds increased maximally immediately after exposure, with partial recovery stabilizing at 7 to 10 days. Correlating with the delayed formation of ROS/RNS, there was a progressive hair cell loss, stabilizing at approximately 2 weeks. Based on these findings, we suggest that initial hair cell damage after noise may primarily reflect mechanical events plus transient intense ROS formation, while continued formation of ROS/RNS contributes to the long-term hair cell loss. The late formation of free radicals may provide a window of opportunity for pharmacological rescue immediately following exposure, requiring both ROS and RNS scavengers.
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, USA.
Daisuke
D
Yamashita
Hong-Yan
HY
Jiang
Jochen
J
Schacht
Josef M
JM
Miller
D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology; D008297:Male; D009622:Noise / Q000009:adverse effects*; D013997:Time Factors
D005609:Free Radicals