Effects of delayed and extended antioxidant treatment on acute acoustic trauma

Abstract

Objective: Hair cell death caused by acute acoustic trauma (AAT) reaches a secondary maximum at 7–10 days after noise exposure due to a second oxidative stress. Therefore, this study tested the effects of a combination of hydroxylated alpha-phenyl-tert-butylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) on AAT when the duration of treatment was extended over the period of 7–10 days after noise exposure as well as when the initial treatment was delayed 24 to 48 h after noise exposure. Methods: Thirty chinchilla were exposed to a 105 dB octave-band noise centred at 4 kHz for 6 h and received the following treatments: (1) noise + saline (2–5) 4-OHPBN (20 mg/kg) + NAC (50 mg/kg) + ALCAR (20 mg/kg) intraperitoneally injected beginning 24 or 48 h after noise exposure twice daily for the next 2, 8 or 9 days. Auditory brainstem response (ABR) threshold shifts, outer hair cell (OHC) counts and organ of Corti immunohistochemistry were analyzed. Results: The combination administration decreased ABR threshold shifts, inhibited OHC loss and reduced 4-hydroxynonenal (4-HNE) immunostaining. Significant decreases in the threshold shifts and reduction in OHC loss were observed with a shorter delay before starting treatment (24 h) and longer duration (9 days) treatment. Conclusions: These results demonstrate that the administration of antioxidant drugs extended up to 10 days after noise exposure can effectively treat AAT in a chinchilla model. This may provide significant and potentially clinically important information about the effective therapeutic window for AAT treatment.

Key Words::

• Hearing loss
• antioxidant drugs
• hydroxylated alpha-tert-butylnitrone (4-OHPBN)
• N-acetyl-L-cysteine (NAC)
• acetyl-L-carnitine (ALCAR)
• auditory brainstem response (ABR)
• outer hair cell loss
• 4-hydroxy-2-nonenal (4-HNE)
• nitrotyrosine (NT)

Acknowledgements

The authors thank Anita Montgomery for her help in the preparation of this manuscript. In addition, we like to thank Angelica Vasquez-Weldon for her help in the preparation of 4-OHPBN.

Conflict of interest

None. This study was supported by grants from the Office of Naval Research and INTEGRIS Health, Oklahoma City, Oklahoma.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Departments of the Navy, Army, Defense or Government of USA.

This paper was first published online on Early Online on 10 August 2011.