Preliminary Study of the Therapeutic Effect of a Nitrone-Based Antioxidant Drug (HPN-07) on Acute Acoustic Trauma

Prof. Chul-Hee Choi, PhD, Department of Audiology and Speech-Language Pathology and Research Institute of Biomimetic Sensory Control, College of Medical Sciences, Catholic University of Daegu, 5 Gumgokri, Hayangup, Kyungsansi, Kyungsangbukdo, Korea e-mail: [email protected] tel.: +82 53 850 3185 Background & Objectives: Acute acoustic trauma (AAT) results in oxidative stress exceeding the capacity of the antioxidant defense mechanisms in cochlea by excessive production of reactive oxygen species, reactive nitrogen species, and other free radicals. Pharmacological approaches have been developed to prevent or treat cochlear injury induced by AAT. The present study aims to investigate if another nitrogen-based antioxidant drug, HPN-07 [a derivative of 4-hydroxy phenyl-N-tert-butyl Nitrone (4-OHPBN)] can be used to treat the permanent hearing loss induced by AAT. Method: Eighteen female chinchillas (six for each group) were exposed to a 105 dB octave-band noise centered at 4 kHz for 6 h. HPN-07 and HPN-07 plus N-acetyl-L-cystein (NAC) were orally administered to two experimental groups giving a first injection 4 h after noise exposure and continually injecting twice daily for the next two days. Auditory brainstem responses (ABR) before noise exposure and 21 days after noise exposure were obtained and analyzed for permanent hearing threshold shifts. Results: Results showed that the mean permanent hearing threshold shifts averaged at higher frequencies (2-8 kHz) for HPN-07 treated group (26 dB) and HPN-07 plus NAC treated groups (11 dB) were significantly decreased compared to the noise exposure group (control group, 36 dB). In addition, significant differences between HPN-07 treated group and HPN-07 plus NAC treated groups were also found. Discussion & Conclusion: HPN-07 reduced permanent hearing threshold shifts and HPN-07 plus NAC showed greater effects. These results demonstrate that HPN-07 and the combination of HPN-07 with NAC can treat acute acoustic trauma and the drug combination increase the therapeutic effect. The therapeutic effect of HPN-07 may result from its role as a free radical scavenger. (Korean Journal of Communication Disorders 2011;16;202-210)