Chronopharmacological Interventions for the Successful Treatment of Noise-Induced Hearing Loss
Abstract
Specific Objective: The present project is based on the unique and exciting findings demonstrating that (1) the amount of noise-induced hearing loss depends on the time of day when the exposure occurs and (2) successful pharmacological treatment for hearing loss depends on the time of the day when the treatment is administered. Aim 1: To determine if sensitivity to different types of noise traumas (permanent, impulse or temporary) depends on the time of day when the exposure occurs (day or night). Aim 2: To determine if pharmacological agents when delivered either before or after the day noise or night noise can protect against the noise traumas mention in Aim 1. Rationale: Our recently published findings showed that night noise trauma was more damaging than day noise trauma in mice. The noise trauma used in that study was inducing a temporary threshold shift. It is now important to extend these original findings to other types of noise damage to determine the generality of circadian regulation of noise-induced hearing loss. Applicability of the proposed findings: Our studies are now opening a new area of research, namely, "chronoaudiology" (time of day when the effectiveness of drug treatment is optimal), a totally unexplored area for the auditory system. Our studies have shown the importance of choosing the appropriate time of the day for pharmacological treatment against noise-induced hearing loss so that treatment can be used with optimal efficacy and minimum toxicity. It is expected that these chrono-approaches may even have applications for other hearing disorders including ototoxicity, inflammation, Ménières disease, and aging. What types of patient will it help and how will it help them? Our findings could have important implications with reference to the circadian variation in the potential for recovery from noise trauma that may play a role for people working in noisy environments, shift workers, and flight crews that frequently travel across time zones and for those who recurrently visit night clubs. Furthermore, the findings from the studies described here have an obvious and important practical implication for human health. Noise levels at work are controlled by a complex legal framework, which defines tolerable levels and requires the wearing of protective hearing devices. To what extent has such legislation accounted for possible circadian effects in man, and would it not now be important to assess whether shift-workers are especially vulnerable? The current statistics related to noise-induced injury for military personnel are devastating. According to the Department of Defense Hearing Center, the Department of Veterans Affairs (VA) spent an estimated $1.39 billion in calculated compensation for major auditory disabilities in fiscal year 2010. The auditory system accounts for the second highest affected body system in VA-disabled Veterans. Tinnitus and hearing loss account for the two most prevalent Service-connected disabilities among Veterans and is increasing by 18% annually. More than 250,000 Service members have reported hearing loss following redeployment from the Gulf War conflicts. In short, these statistics are alarming and clearly indicate that new strategies for avoiding these hearing disorders are needed immediately. What are the potential clinical applications, benefits and risks? An immediate clinical benefit from this study is an increased awareness for the time of day for when pharmacological agents would have optimal effect for treating hearing disorders. In other systems (i.e., liver, kidney) it has been known for more than 30 years that drug absorption and distribution are subjected to diurnal variations in rodents and humans. A 24-hour change in drug bioavailability has therefore been established for hundreds of drugs. For example, acetaminophen (3) and theophylline (3) show different pharmacokinetics in the morning compared with the evening. Our findin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610032
Entities
People
- Barbara Canlon
Organizations
- Karolinska Institutet
- United States Army