We have previously used a three antioxidant combination [4-hydroxy phenyl N-tertbutylnitrone
(4-OHPBN), N-acetyl-L-cysteine (NAC), Acetyl-L-carnitine (ALCAR)] to successfully treat
acute acoustic trauma (AAT) in chinchilla. However, the mechanistic basis of these antioxidants in
treating AAT has not yet been resolved at the cellular and molecular levels. In the present study, we
exposed chinchilla to 105 dB SPL octave-band noise centered at 4 kHz for 6 hours. One group of
chinchilla was treated with the three antioxidants beginning 4 hour after noise exposure. Auditory
brainstem responses, outer hair cell counting and semi-quantitative immunohistochemical analyses of
biomarkers in the cochlea was used to evaluate effectiveness of the antioxidant treatment in AAT. The
antioxidant treatment significantly reduced hearing threshold shifts, outer hair cell loss, number of
CD45+ cells in the stria vascularis, as well as 4-hydroxy-2-nonenal and nitrotyrosine formation in the
cochlea. The antioxidant treatment provides not only direct protection to sensory cells by inhibiting
formation of ROS in the organ of Corti but also indirect protection to these cells by reducing formation
of RNS and migration of mononuclear phagocytes in the lateral wall. The present study provides direct
evidence of effectiveness of antioxidant treatment and its underlining mechanisms in AAT.