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Title: Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats

Abstract

The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparationsmore » of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the main target of toxicity. While the exact mechanism is unknown, the results are consistent with the hypothesis of ROS involvement in NIHL at moderate levels.« less

Authors:
 [1];  [2];  [2]
  1. Jerry Pettis Memorial Veterans Medical Center, Research Service (151), Loma Linda, CA 92357 (United States). E-mail: benoit.pouyatos@med.va.gov
  2. Jerry Pettis Memorial Veterans Medical Center, Research Service (151), Loma Linda, CA 92357 (United States)
Publication Date:
OSTI Identifier:
20721776
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 204; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2004.08.015; PII: S0041-008X(04)00392-8; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACRYLONITRILE; ANTIOXIDANTS; AUDITORY ORGANS; BIOLOGICAL STRESS; DAMAGE; GLUTATHIONE; HAIR; NOISE; RATS; SUPEROXIDE DISMUTASE; TOXICITY

Citation Formats

Pouyatos, BenoIt, Gearhart, Caroline A., and Fechter, Laurence D. Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats. United States: N. p., 2005. Web. doi:10.1016/j.taap.2004.08.015.
Pouyatos, BenoIt, Gearhart, Caroline A., & Fechter, Laurence D. Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats. United States. doi:10.1016/j.taap.2004.08.015.
Pouyatos, BenoIt, Gearhart, Caroline A., and Fechter, Laurence D. Fri . "Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats". United States. doi:10.1016/j.taap.2004.08.015.
@article{osti_20721776,
title = {Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats},
author = {Pouyatos, BenoIt and Gearhart, Caroline A. and Fechter, Laurence D.},
abstractNote = {The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparations of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the main target of toxicity. While the exact mechanism is unknown, the results are consistent with the hypothesis of ROS involvement in NIHL at moderate levels.},
doi = {10.1016/j.taap.2004.08.015},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 204,
place = {United States},
year = {Fri Apr 01 00:00:00 EST 2005},
month = {Fri Apr 01 00:00:00 EST 2005}
}
  • The present study assessed the relationships among occupational noise exposure, noise-induced hearing loss, and high blood pressure. The study population consisted of 245 retired metal assembly workers from Pittsburgh aged 56 to 68 with chronic noise exposure of 30 or more years at greater than or equal to 89 dBA. Results of the audiometric testing indicated 52% of the younger workers (ages 56 to 63) have severe noise-induced hearing loss (greater than or equal to 65 dBA loss at 3, 4, or 6 kHz) and 67% of older workers (ages 64 to 68). Body mass index and alcohol intake weremore » significantly related to systolic and diastolic blood pressure. Among older men, there was a marginally significant increased prevalence of high blood pressure (greater than or equal to 90 mm diastolic or taking blood pressure medicine) among those with severe noise-induced hearing loss (P = .05). Moreover, another measure of hearing loss at high frequencies, speech discrimination score in noise (measured in the better ear), referred to as the W-22 MAX score, was also found to be related to the prevalence of high blood pressure in the older (64 to 68) age group (P less than .05). Multiple regression analysis revealed W-22 MAX and severe noise-induced hearing loss were independent predictors of hypertension in the older, but not in the younger group of retired workers.« less
  • Purpose: To determine the effect of cochlear dose on sensorineural hearing loss in pediatric patients with brain tumor treated by using conformal radiation therapy (CRT). Patients and Methods: We studied 78 pediatric patients (155 ears) with localized brain tumors treated in 1997-2001 who had not received platinum-based chemotherapy and were followed up for at least 48 months. They were evaluated prospectively by means of serial pure-tone audiograms (250 Hz-8 kHz) and/or auditory brainstem response before and every 6 months after CRT. Results: Hearing loss occurred in 14% (11 of 78) of patients and 11% (17 of 155) of cochleae, withmore » onset most often at 3-5 years after CRT. The incidence of hearing loss was low for a cochlear mean dose of 30 Gy or less and increased at greater than 40-45 Gy. Risk was greater at high frequencies (6-8 kHz). In children who tested abnormal for hearing, average hearing thresholds increased from a less than 25 decibel (dB) hearing level (HL) at baseline to a mean of 46 {+-} 13 (SD) dB HL for high frequencies, 41 {+-} 7 dB HL for low frequencies, and 38 {+-} 6 dB HL for intermediate frequencies. Conclusions: Sensorineural hearing loss is a late effect of CRT. In the absence of other factors, including ototoxic chemotherapy, increase in cochlear dose correlates positively with hearing loss in pediatric patients with brain tumor. To minimize the risk of hearing loss for children treated with radiation therapy, a cumulative cochlear dose less than 35 Gy is recommended for patients planned to receive 54-59.4 Gy in 30-33 treatment fractions.« less
  • Recent studies of health effects from chronic exposure to noise in the workplace have not consistently addressed nonoccupational variables. A cross-sectional study was conducted with 197 randomly selected male hourly workers from a noisy plant ( greater than or equal to 89 dBA) in Pittsburgh to fully assess noise exposure and hearing loss, incorporating information on duration of exposure, noise level, occupational and medical histories, audiometric evaluation, and external noise sources. Population audiometric profiles are characteristic of noise-induced hearing loss; mean hearing thresholds for press room men were significantly higher at 2, 3, and 6 kHz (p less than ormore » equal to .05). Only 40% of the men consistently wore hearing protection. Recent use of ototoxic drugs, noisy hobbies/second jobs, military service, family history of hearing loss, and ear-related problems were not found to have a significant effect on hearing levels at high frequencies, suggesting that observed hearing losses were of an occupational origin. 31 references, 3 figures, 3 tables.« less
  • The effect of 60 minutes of exposure to high-frequency (10- to 40-kHz), high-intensity (115-dB) noise on the cochlear blood flow (CoBF) was investigated in adult gerbils. The CoBF was measured with a newly improved microsphere method. The number of microspheres in cochlear tissue that had been dissected by the surface preparation technique was assessed by direct counting. Our experiments have indicated that the CoBF is elevated even after 60 minutes of noise exposure. This was true particularly in the areas where these frequencies stimulate the cochlea. The noise also increased CoBF in the opposite ear in areas not corresponding tomore » the stimulation frequencies (second and third turn). This phenomenon is under further investigation.« less
  • Hearing loss affects 30 million people in the United States; of these, 21 million are over the age of 65 years. This disorder may have several causes: heredity, noise, aging, and disease. Hearing loss from noise has been recognized for centuries but was generally ignored until some time after the Industrial Revolution. Hearing loss from occupational exposure to hazardous noise was identified as a compensable disability by the United States courts in 1948 to 1959. Development of noisy jet engines and supersonic aircraft created additional claims for personal and property damage in the 1950s and 1960s. These conditions led tomore » legislation for noise control in the form of the Occupational Safety and Health Act of 1970 and the Noise Control Act of 1972. Protection of the noise-exposed employee was also an objective of the Hearing Conservation Act of 1971. Subsequent studies have confirmed the benefits of periodic hearing tests for workers exposed to hazardous noise and of otologic evaluation as part of the hearing conservation process. Research studies in laboratory animals, using scanning electron microscopical techniques, have demonstrated that damage to the inner ear and organ of hearing can occur even though subjective (conditioned) response to sound stimuli remains unaffected. Some investigators have employed an epidemiologic approach to identify risk factors and to develop profiles to susceptibility to noise-induced hearing loss. The need for joint involvement of workers and employers in the reduction and control of occupational noise hazards is evident. 19 references.« less