Acrylonitrile potentiates noise-induced hearing loss in rat

Abstract

Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl- N- tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.

Figure 1

Exposure chamber noise spectral analysis conducted using 1/3 octave band filter system under conditions of noise exposure and quiet (ambient noise).

Figure 2

Promotion of noise-induced hearing loss assessed four weeks following a single exposure to acrylonitrile (50 mg/kg sc), noise (4 h 105 dB octave band noise), combined exposure to ACN followed 1 h later by noise exposure, and no experimental treatment. While noise alone elevated thresholds for high-frequency tones, the ACN treatment was able to significantly enhance this threshold shift. Acrylonitrile by itself did not produce a permanent threshold shift.

Figure 3

Promotion of noise-induced hearing loss assessed four weeks following the last of five daily exposures to ACN (50 mg/kg sc), noise (4 h 105 dB octave band noise), combined exposure to ACN followed 1 h later by noise exposure, and no experimental treatment. While noise alone elevated thresholds for high-frequency tones, the ACN treatment was able to significantly enhance this threshold shift. Acrylonitrile by itself did not produce a permanent threshold shift.

Figure 4

Protective effects of PBN (2 × 100 mg/kg IP) against the promotion of noise-induced hearing loss by ACN (50 mg/kg sc) + noise (105 dB OBN 4 h) given on five successive days. Thresholds were assessed four weeks later. PBN was administered 60 min prior to ACN and, again, immediately following termination of noise exposure.

Figure 5

Effect of PBN (2 × 100 mg/kg IP) against noise-induced hearing loss (105 dB OBN 4 h) given on five successive days. Thresholds were assessed four weeks later. PBN was administered 120 min prior to noise and, again, immediately following termination of noise exposure. PBN administration on this schedule failed to reduce the extent of noise-induced hearing loss.