Donald Henderson - donaldhe@acsu.buffalo.edu
Bo-Hua Hu
Sandra L. McFadden
Center for Hearing and Deafness
University at Buffalo
Buffalo, NY 14214
Howard Steinman
Albert Einstein College of Medicine
Bronx, NY
Richard Kopke
Naval Medical Center
San Diego, CA
Popular version of paper 3aNSa4
Presented Wednesday morning, June 18, 1997
133rd ASA/NOISE-CON 97 Meeting, State College, Pennsylvania
Embargoed until June 18,1997
Exposure to high-level noise in the workplace presents a significant health problem for approximately nine million Americans. People are also placed at risk for developing noise-induced hearing loss (NIHL) in the military and when they participate in noisy recreational activities, such as car racing, snowmobiling, shooting firearms, and listening to loud music. The use of personal protection devices (PPDs)--earmuffs and insert earplugs--can reduce or prevent NIHL in many situations. Unfortunately, there are times when people either can not or do not use PPDs, or when exposure to damaging levels of noise cannot be avoided. What is interesting is that some people will develop a large amount of permanent hearing loss, while others will develop little or no hearing loss after exposure to the same noise.
Until very recently, the prevailing view was that susceptibility to NIHL could be related to relatively fixed factors, such as the length and resonant properties of the ear canal, the presence of melanin in the skin, and the effectiveness of the acoustic reflex. As a result of recent experiments, we now know that individuals' susceptibility to NIHL can be influenced by their prior noise-exposure history, and that the amount of damage resulting from high-level noise exposure can be either increased or decreased by manipulating the ear's natural defense systems. Our recent studies on acquired resistance to noise (ARN) and the role of the antioxidant defense system in modulating noise damage may shed some light on both the source of individual differences in susceptibility and the biological processes involved in NIHL.
The idea that individuals' susceptibility to NIHL can be influenced by their prior exposure history can be traced to a series of experiments done at the Karolinska Institute in Stockholm with guinea pigs, and parallel experiments at the Center for Hearing and Deafness in Buffalo, New York with chinchillas. When chinchillas are exposed to a low-frequency noise (0.5 kHz octave band noise) at a moderate level of 95 dB for 6 hours per day for 10 days, they develop an average of 45 dB temporary threshold shift (TTS) after the first day's exposure. By the fifth day of exposure, the average TTS drops to only 20 dB. The decrease in TTS with repeated exposures has been referred to as "conditioning" or "toughening." When "conditioned" subjects are subsequently exposed to the same low-frequency noise, but at a higher level of 105 dB, they develop 10 to 20 dB less permanent threshold shift (PTS) than control subjects who only received the high-level exposure. We refer to the phenomenon whereby subjects become more resistant to permanent hearing loss following conditioning exposures as "acquired resistance to noise." The conditioning and ARN phenomena appear to be part of a general response of the mammalian auditory system, because similar results have been reported for guinea pigs, rabbits and in terms of TTS, for humans as well.
In other experiments, we have learned that ARN can last at least 60 days. The persistence of ARN may be a clue that the conditioning exposures alter a fundamental facet of inner ear physiology. During exposure to high levels of noise, one of the damaging events that is likely to occur is an increased production of free radical molecules. The free radicals can cause serious damage to cells unless they are "neutralized" by free radical scavengers. For noise exposures that are not damaging, it is hypothesized that free radical scavengers are produced at a rate that is adequate to neutralize the cytotoxic free radicals. For noise exposures that lead to permanent hearing loss, however, cytotoxic free radicals may be generated at a rate that exceeds the ear's ability to neutralize them.
Given that conditioning exposures render the inner ear more resistant to noise, and that free radical scavengers may influence the degree of damage after noise exposure, we were interested in learning the status of the free radical defense system before and after conditioning exposures. What we discovered was that the most common and perhaps the most important antioxidant enzyme, glutathione, and related enzymes, glutathione reductase and g-glutamyl cysteine synthetase, were dramatically increased in animals that had the conditioning exposure and then were exposed to a high-level traumatic exposure. The high levels of the antioxidant enzymes suggest that the inner ear levels of these enzymes can be increased by conditioning, and that they are involved in protecting the ear from noise trauma.
To further test the importance of glutathione in ARN, a second experiment was conducted in which the left ears of chinchillas were given a drop of saline and the right ears a drop of R-PIA, a drug that upregulates or increases the concentration of glutathione. After the drug treatment, the subject was exposed to high-level noise. We found that ears treated with R-PIA had less PTS and inner ear pathology than ears treated with saline.
To better understand the role of the free-radical scavenger system in NIHL, a third group of chinchillas was exposed to a traumatic noise and then their inner ears were harvested at various times after the noise exposure and stained for glutathione. Two inner ears are shown in the figure below. The ear shown on the left is from a normal chinchilla. Glutathione is found at the membrane and below the stereocilia of the outer hair cells. The ear shown on the right is from a noise-exposed chinchilla. Here, the sensory hair cells are distorted and the concentration of glutathione is markedly reduced in many of the cells. These pictures suggest that degeneration of the inner ear following noise exposure is associated with depletion of the free radical scavenger molecules.
Collectively, these experiments suggest that the antioxidant system is an important factor in the ear's resistance to noise and that the effectiveness of the antioxidant system can be enhanced by prophylactic conditioning noise exposures and by direct pharmacological interventions. From a practical point of view, these principles might be applied to developing ways of protecting individuals from permanent hearing loss when they cannot use personal protection devices.