Therapeutic effect of combined antioxidant drugs (4-OHPBN plus NAC) onacute acoustic trauma in terms of distortion product otoacoustic emission

Therapeutic effect of combined antioxidant drugs (4-OHPBN plus NAC) on acute acoustic trauma in terms of distortion product otoacoustic emission Chul-Hee Choi Department of Audiology and Speech-Language Pathology, College of Medical Sciences, Catholic University of Daegu, Kyung-Buk, Korea Research Institute of Biomimetic Sensory Control, Catholic University of Daegu, Kyung-Buk, Korea Acute acoustic trauma (AAT) induces hearing loss through the primary hair cell death pathway called apoptosis. The hair cell death occurs by over-production of reactive oxygen species, reactive nitrogen species, and other free radicals, which result from oxidative stress destroying the antioxidant defense mechanisms in the cochlea. Pharmacological approaches have been developed to prevent or treat cochlear damage induced by AAT. The objective of this study is to investigate the therapeutic effect of the combined antioxidant drugs (4-OHPBN plus NAC) in treating hearing loss induced by AAT when these drugs are orally administered. Thirty female chinchillas (six for each group) were exposed to a 105 dB SPL octave-band noise centered at 4 kHz for 6 hours. A combination of 4-hydroxy phenyl-N-tert-butylnitrone (4-OHPBN) plus N-acetyl-L-cystein (NAC) were orally administered to all experimental groups giving a first injection 4 hour after noise exposure and continually injecting twice daily for the next two days. Cubic distortion product otoacoustic emissions (DPOAE) before noise exposure and 21 days after noise exposure were obtained and statistically analyzed. The cubic DPOAE amplitudes were significantly different among different groups at different frequencies. The oral administration of 4-OHPBN plus NAC significantly increased permanent DPOAE amplitude. The increase was partially correlated with the dose of 4-OHPBN plus NAC. These results demonstrate that the combination of 4-OHPBN plus NAC can treat acute acoustic trauma although these drugs are orally administered. At the high dose of 4-OHPBN (75 mg/kg) plus NAC (200 mg/kg), the cubic DPOAE amplitude was reduced compared to those of 4-OHPBN (50 mg/kg) plus NAC (100 mg/kg). This reduction indicates that the only highest dose of 4-OHPBN may be ototoxic.