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This Article Full Text Full Text (PDF) All Versions of this Article: 93/4/2053    most recent 00959.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Huang, Z.-W. Articles by Zhao, H.-B. Search for Related Content PubMed PubMed Citation Articles by Huang, Z.-W. Articles by Zhao, H.-B.

Paradoxical Enhancement of Active Cochlear Mechanics in Long-Term Administration of Salicylate

¹Department of Otolaryngology, People's Hospital, Faculty of Medicine, Wuhan University, Wuhan, China; and ²Department of Surgery–Otolaryngology, University of Kentucky Medical Center, Lexington, Kentucky

Submitted 15 September 2004; accepted in final form 1 December 2004

Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment, the effects of long-term salicylate administration on cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f₁-f₂ within 2 h. The reduction was significant at 20–50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f₁-f₂ progressively increased. After injection for 14 days, the distortion product increased about 2–3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40–70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level.