Abstract
Noise-induced hearing loss (NIHL) is an important occupational disorder. However, the molecular mechanisms underlying NIHL have not been fully clarified; therefore, the condition lacks effective therapeutic methods. Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the synthesis of prostaglandins, and has been implicated in many pathophysiological events, such as oxidative stress and inflammation. In this study, we investigated the possible role of Cox-2 in the mechanisms of NIHL and the therapeutic effect of the Cox-2 inhibitor NS398 on NIHL using a mouse model. We demonstrated that Cox-2 is constitutively expressed in the mouse cochlea, and its expression could be dramatically up-regulated by high levels of noise exposure. Furthermore, we demonstrated that pre-treatment with the Cox-2 inhibitor NS398 could inhibit Cox-2 expression during noise overstimulation; and could attenuate noise-induced hearing loss and hair cell damage. Our results suggest that Cox-2 is involved in the pathogenesis of NIHL; and pharmacological inhibition of Cox-2 has considerable therapeutic potential in NIHL.
Highlights
Noise-induced hearing loss (NIHL) is one of the most prevalent occupational disorders in the world
We found that Cox-2 was constitutively expressed in the mouse cochlea, and its expression could be dramatically up-regulated by high levels of noise exposure
We demonstrated that pre-treatment with the Cox-2 inhibitor NS398 could inhibit Cox-2 expression induced by acoustic injury and could attenuate noise-induced hearing threshold shifts and cochlear hair cell loss
Summary
Noise-induced hearing loss (NIHL) is one of the most prevalent occupational disorders in the world. One study showed that Cox-2 expression in the organ of Corti could be down-regulated by moderate sound exposure designed to produce sound conditioning, and the author hypothesized that the alteration of Cox-2 might be part of the sound conditioning effect (sound conditioning refers to the acquired resistance to NIHL caused by pre-exposure to low level non-traumatic noise)[10,28]. This finding suggests a potential role for Cox-2 to mediate the responses of cochlea to acoustic injury. We investigated whether NIHL is associated with up-regulation of the Cox-2 and if so, we sought to define whether Cox-2 expression contributes to noise-induced hearing threshold shifts and hair cell death by the pharmacological inhibition of Cox-2 expression
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