Hearing Professional Center
By: Allison McKenzie , Au.D.
Doctor of Audiology
5462 Glen Lakes Drive
Dallas, TX 75231
(214) 987-4114
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www.hearing-center.com

Noise induced hearing loss (NIHL) is the second most common cause of sensorineural hearing loss (SNHL) in industrialized societies. Excessive noise exposure is the only preventable cause of SNHL (Kopke, 2007). The hair cells of the inner ear are the specific structures damaged by excessive noise exposure and, in mammals, are unable to regenerate spontaneously. This physical damage can cause permanent and irreversible hearing loss as well as degrade a person’s quality of life. Knowing how the physical structure is affected by noise can aid researchers in their search for therapeutic agents that act as otoprotectants against NIHL (Ciorba et al, 2008). Personal hearing protection devices along with environmental engineering are the most prevalent protection methods of hearing conservation programs. Even with the required participation in hearing conservation programs, by workers who are exposed to noise at or above the action level, NIHL is still quite common. The current methods of protection are limited in their ability to save every listener from a NIHL. Researchers are actively searching for a pharmacologic approach that, when combined with environmental engineering and personal hearing protection devices, will more completely protect people from NIHL (Kopke, 2007).

Antioxidants

Vitamin E

Oxidative stress has been proven to contribute to the degradation of hair cells in the cochlea. Drugs with antioxidant properties, such a vitamin E, have been tested on both animals and humans. The success with vitamin E as an otoprotectant in animals is far greater than the results seen is human subjects. The different effects of antioxidants between human and animal subjects may be due to differences in pharmacokinetic and pharmacodynamic principles. More research is needed to determine when and in what intervals antioxidant treatments are needed to be the most useful in preventing NIHL in humans (Fetoni et al, 2008).

N-acetyl-l-cysteine (NAC)

The glutathione pathway is a very important antioxidant pathway in the cochlea. NAC acts as a glutathione substrate and aids the body in glutathione synthesis. Research shows the effectiveness NAC has on NIHL when given intraperitoneally and via oral gavage. ABR recordings on chinchillas show the differences between dosing methods and different types of noise exposure. Many studies have shown the otoprotectant effectiveness of NAC in animal subjects, but this particular study chose to administer high-kurtosis noise in order to simulate a typical industrial environment. The goal was to show whether NAC would be considered an effective treatment method in human subjects with a NIHL (Bielefeld et al, 2007).

Clifford and Rogers (2009) looked at the effect of antioxidants as otoprotectants for impact noise trauma. They stated that people who are exposed to impact noise are at greater risk for NIHL. They chose to study the otoprotectant effect of NAC on chinchillas. The antioxidant effected the way the cochlea reacted to changes in oxygen and nitrogen which helped protect the inner ear from severe hair cell damage. There were limitations to this study due to the difficulty the researchers faced when trying to measure the physical changes during impulse noise stimulation. Clifford and Rogers (2009) cite the work of Kopke’s unpublished pilot study of 566 Marine recruits which reported a 25% reduction in the number of Marines suffering a NIHL after a two-week period of M16 rifle exposure. These Marines were given NAC as the antioxidant otoprotective agent. There is more research on the usefulness of antioxidants as otoprotectants currently being conducted with military personnel.

A study conducted in 2006 looked at NAC given thirty minutes prior to exposure to loud music. This is the only study that administered the NAC by effervescent tablet form. The results indicated that the results from the NAC group were no different than the results from the placebo group. The author pointed out other research that suggests dosing schedule is very important to the success of NAC in preventing permanent threshold shifts (Kramer et al, 2006).

HPC Staff: (From Left) Dr. Allison McKenzie, Jared Lacy & Dr. Deborah Price

C-Jun N-terminal Kinase (JNK) Inhibitors

JNKs are stress activated protein kinases that have been shown to be responsible in the apoptosis or death of oxidative stress-damaged cells. Knowing the signaling chain of JNKs can effectively help researchers provide otoprotectants that are efficient in preventing cochlear damage. JNK inhibitors are cell permeable peptides that target specific protein groups and block the JNK from carrying out its natural course in the cell. One research study showed that the  peptide conjugate D-JNKI-1 can be injected locally to the scala tympani of explanted cochleas to provide protection from acoustic trauma as well as aminoglycosides. JNK inhibitors as otoprotectants have shown the ability to keep a temporary threshold shift from becoming a permanent hearing loss (Zine and Van de Water, 2004).

A more recent study looked at the effect of JNK inhibitors on patients whose hearing was affected by firecrackers on New Year’s Eve. The 11 subjects were selected within 24 hours of the firecracker display and had at least a 30 dBHL loss at 4 and 6 KHz. The subjects were given topical anesthesia and then given a single intratympanic injection of either .4 or 2.0 g/ml of the JNK inhibitor AM-111. The results showed no difference between the dosage groups. The study shows improvement in the thresholds of all 11 subjects, but there was not a control group to compare these results to. There is not enough evidence to say that AM-111 should be used clinically to treat acute acoustic trauma (Suckfuell et al, 2007).

Coenzyme Q10

Coenzyme Q10, which is used to increase cellular metabolism, was used to determine otoprotective effectiveness in 30 guinea pigs. The coenzyme Q10 was given intraperitoneally 2 hours before the guinea pigs were exposed to 130 dBSPL of noise centered at 4 KHz for 3 hours. ABR was used to measure pre and post results. The guinea pigs showed no differences in ABR recordings prior to noise exposure, but 7 days after the exposure the treatment group showed less of a shift than the control group. There was a marked improvement in antioxidative activity noticed 2 days post coenzyme Q10 injection (Hirose et al, 2008).

Hepatocyte Growth Factor (HGF)

HGF is a protein responsible for cell growth and different morphogenic factors. Gelatin hydrogels that had been dipped in either HGF or saline were placed on the round window of 18 guinea pigs 1 hour after a 3 hour exposure to 120 dBSPL noise. The results were measured using ABR throughout the testing process. The ABR results showed that the guinea pigs who were given the gelatin hydrogels dipped in HGF had better ABR thresholds than the saline group. The results differed in the basal portion of the cochlea only. The apical region remained unchanged for both groups (Inaoka et al, 2009).

Tacrolimus (TCR) and Melatonin (MLT) vs. Dexamethasone (DXM)

A recent study compared TCR, MLT and DXM under the same conditions to determine which if any was the most effective otoprotectant. TCR is a calcineuron inhibitor that was administered to a group of rats the day before exposure to traumatic noise and for 14 days following the noise exposure. The TCR group of rats showed an improvement in ABR thresholds within one week post noise exposure. The rats given MLT, a pineal gland hormone and antioxidant, were reported to show a marked improvement in ABR thresholds by week three post noise exposure. The group given DXM, an anti-inflammatory and immunosuppressant, showed no difference in ABR threshold recordings from the control group (Bas et al, 2009).

Implications

Most of the research on otoprotectants that has been published is based on an animal model. There are a few human subject based articles, but the methods of otoprotectant use are varied. The study that looked at the effect of NAC on people exposed to loud music used an effervescent tablet. I question whether the outcome would have been different if the dosing method had been different. My concern is the feasibility of intratympanic injections every time a person is exposed to excessive amounts of noise. More research is needed to determine which of the treatments presented in this paper are useful clinically. Every research article mentioned the need for more research to fully understand how the system works. I would like to see more human subject research to better understand how an otoprotectant might be most effective.