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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
The non-steroidal anti-inflammatory drugs protect mouse cochlea against acoustic injury
Tomofumi Hoshino1, Keiji Tabuchi, Yuki Hirose
1Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Abstract:
Acoustic injury is a common cause of hearing loss for people in industrial societies. Cyclooxygenase (COX) and lipoxygenase (LOX) are two important enzymes involved in arachidonic acid metabolism. Two COX isozymes are characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression. Although COX-1, COX-2, and LOX are expressed in cochlea, their roles played in cochlear acoustic injury have not fully been evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit either COX or LOX, or both. This study evaluated the effects of NSAIDs on the functional recovery of the cochlea after acoustic injury. Mice were exposed to a 4-kHz pure tone of 128 dB SPL (sound pressure level) for 4 hours and received one of the following drugs for two weeks after acoustic overexposure: indomethacin (COX-1 inhibitor), meloxicam, SC58125, and CAY10404 (COX-2 inhibitors), and nordihydroguaiaretic acid (LOX inhibitor). The hearing ability was evaluated using an auditory brainstem response (ABR) before and after overexposure. The ABR threshold shifts, defined as subtraction between ABR thresholds before and after overexposure, were compared among the control and the medication groups at one and two weeks after acoustic overexposure. Treatment of mice with either indomethacin or nordihydroguaiaretic acid decreased the ABR threshold shifts after overexposure, indicating that COX-1 and LOX inhibitors exhibited protective effects against acoustic injury. In contrast, COX-2 inhibitors, meloxicam, SC58125, and CAY10404, showed no noticeable effects on the ABR threshold shifts. These findings suggest that COX-1 and LOX are involved in the pathogenesis of acoustic injury in cochlea.
Insights
Non-steroidal anti-inflammatory drugs targeting cyclooxygenase-1 (COX-1) and lipoxygenase (LOX) enzymes aided hearing recovery after acoustic injury. COX-1 and LOX inhibition protected against cochlear damage, unlike COX-2 inhibitors.
Area of Science:
- Oto-toxicology
- Pharmacology
- Auditory Neuroscience
Background:
- Acoustic injury is a significant cause of hearing loss in industrial societies.
- Cyclooxygenase (COX) and lipoxygenase (LOX) pathways are implicated in arachidonic acid metabolism, with roles in the cochlea not fully understood regarding acoustic injury.
- Non-steroidal anti-inflammatory drugs (NSAIDs) offer potential therapeutic avenues by inhibiting COX or LOX enzymes.
Purpose of the Study:
- To investigate the effects of specific NSAIDs, targeting COX-1, COX-2, and LOX, on the functional recovery of the cochlea following acoustic injury.
- To elucidate the specific roles of COX-1, COX-2, and LOX in the pathogenesis of noise-induced hearing loss.
Main Methods:
- Mice were subjected to acoustic overexposure (4-kHz tone, 128 dB SPL for 4 hours).
- Post-exposure, mice received daily treatments with indomethacin (COX-1 inhibitor), meloxicam, SC58125, CAY10404 (COX-2 inhibitors), or nordihydroguaiaretic acid (LOX inhibitor) for two weeks.
- Auditory brainstem response (ABR) was used to measure hearing thresholds before and after acoustic exposure to assess ABR threshold shifts.
Main Results:
- Treatment with indomethacin (COX-1 inhibitor) and nordihydroguaiaretic acid (LOX inhibitor) significantly reduced ABR threshold shifts, indicating protective effects against acoustic injury.
- COX-2 inhibitors (meloxicam, SC58125, CAY10404) did not demonstrate noticeable effects on ABR threshold shifts.
- These findings suggest differential involvement of COX isoforms and LOX in cochlear response to acoustic trauma.
Conclusions:
- COX-1 and LOX pathways play a significant role in the development of cochlear acoustic injury.
- Targeting COX-1 and LOX, but not COX-2, with NSAIDs may offer a therapeutic strategy for mitigating noise-induced hearing loss.
- Further research into the specific mechanisms of COX-1 and LOX in cochlear damage is warranted.
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