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

Choi, Chul-Hee; Choi, Chul-Hee

ORIGINAL ARTICLE

Commun Sci Disord. 2011;16(2): 202-210.

Chul-Hee Choi^`

최철희(Chul-Hee Choi)

ABSTRACT

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 ㏈ octave-band noise centered at 4 ㎑ 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 ㎑) for HPN-07 treated group (26 ㏈) and HPN-07 plus NAC treated groups (11 ㏈) were significantly decreased compared to the noise exposure group (control group, 36 ㏈). 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.