Noise-induced nitrotyrosine increase and outer hair cell death in the guinea pig cochleaWeiju Hana, *, Xiaorui Shib, and Alfred Nuttallb,c

Objective: To understanding noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in the guinea pig cochlea. Method: Thirty guinea pigs were used in this study. The experement animals were either exposed for 4 h/day to broadband noise at 122 dB SPL (A-weighted) for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of animals were dissected. Propidium iodide (PI), a DNA intercalating fluorescent probe, was used to trace the morphological changes in OHC nuclei. The distribution of nitrotyrosine (NT) in the organ of Corti and the cochlear lateral wall tissue from the guinea pig were examined using the fluorescence immunohistochemistry method.The Whole mounts of organ of Corti was were prepared. Morphological and flourescentfluorescent changes were observed examined use under a confocal microscope. Results: (1) Either after noise exposure or after SIN1 perfusion, outer hair cells(OHCs) death with character of both apoptotic and necrotic were appeared. (2) Nitrotyrosine immunolabeling could be observed in the OHCs from the control animal. After noise exposure, NT immunostaining becames much greater than control animals in OHCs. (3) The in apoptotic OHC has significant increase of nitrotyrosine in and around nucleus following noise exposure. (4) In the the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis.. Conclusion: These findings indicate that the noise exposure injure induced increase of nitrotyrosine production was associate with the OHCs death and suggest that reactive nitrogen species participate in the cochlear pathophysiology of noise-induced hearing loss