Influences of Hypoxia on Noise Induced Hearing Loss

DESCRIPTION (provided by applicant): Noise-induced hearing loss (NIHL) is the most common occupational disease in the United States, yet it's mechanisms are not fully understood. The goal of this application is to determine whether and how hypoxia can interrupt auditory function transiently. People may suffer from insufficient blood oxygen supply due to pulmonary or cardiovascular disease, altitude, and environmental pollution by chemical asphyxiates. The risk of environmental noise may be tremendously increased when the noise is under hypoxic conditions. As indirect evidence, carbon monoxide (CO) exposure, which among other effects reduces oxygen supply to tissues, potentiates permanent NIHL at a level that alone does not cause a permanent threshold loss. The investigation of effect of hypoxic inhalation on NIHL will provide a direct test of the susceptibility of the cochlea to reduced oxygen tension. In this application, noise intensity will be varied from lower than the current permissible exposure level (PEL) to 120 dB SPL. Noise intensity higher than 120 dB SPL may cause some mechanical damage to the cochlea. Oxygen level in the exposure chamber will be varied from the normal level (21%) to 6%. Hypoxic inhalation alone with oxygen level lower than 6% may cause a temporary auditory function loss. The designed experiments will measure: (1) noise-induced and noise+hypoxia-induced hearing loss and hair cell loss 4 weeks after the exposure; (2) free radical generation, succinate dehydrogenase (SDH) activity reduction and apoptotic cell death in the cochlea immediately after the exposure; and (3) time course of these biochemical alterations and the protective effect of a free radical scavenger against SDH-activity reduction and apoptosis. We hypothesize that the noise under hypoxic conditions will generate more free radicals than noise alone, which then impair mitochondria, causing a reduction in SDH activity and also release of cytochrome c that may cause apoptosis. We further hypothesize that free radical scavenging will protect against SDH activity reduction and apoptosis.