Tohoku J. Exp. Med., 2008, 216(1)

The Non-steroidal Anti-inflammatory Drugs Protect Mouse Cochlea against Acoustic Injury

TOMOFUMI HOSHINO,¹ KEIJI TABUCHI,¹ YUKI HIROSE,¹ ISAO UEMAETOMARI,¹ HIDEKAZU MURASHITA,¹ TADAMICHI TOBITA¹ and AKIRA HARA¹

¹Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

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.

keywords —— cyclooxygenase; lipoxygenase; non-steroidal anti-inflammatory drugs; cochlea; acoustic injury.

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 216, 53-59

Correspondence: Keiji Tabuchi, Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.

e-mail: ktabuchi@md.tsukuba.ac.jp