• Kai Helling, Karl Wodarzcyk, Jürgen Brieger, Irene Schmidtmann, Huige Li, Wolf J Mann, and Ulf-Rüdiger Heinrich.
• Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, Mainz, Germany. kai.helling@unimedizin-mainz.de
• Auris Nasus Larynx. 2011 Dec 1;38(6):671-7.

ObjectiveGentamicin application is an important therapeutic option to control vertigo spells in Ménière's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin.MethodsIn a prospective animal study, a single dose of gentamicin (10mg/kg body weight) was injected intratympanically into male guinea pigs (n=48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards. The organ of Corti and the lateral wall of 42 animals were isolated after 7 days and incubated separately for 6h in cell culture medium. Doxycycline was adjusted to organ cultures of 5 animals. Two NOS inhibitors, N(G)-Nitro-l-arginine methyl ester (l-NAME) and NG-monomethyl-l-arginine monoacetate (l-NMMA), were applied in three different concentrations to the organ cultures of 30 animals in total (5 animals per concentration). As controls, seven animals received no further substance except gentamicin. The NO-production was quantified by chemiluminescence. Additional six gentamicin-treated animals were used for immunohistochemical studies.ResultsThe ABRs declined continuously from the first to the seventh day after gentamicin application. Doxycycline reduced NO-production in the lateral wall by 54% (p=.029) comparable to the effect of the applied nitric oxide inhibitors. In the organ of Corti, NO-production was reduced by about 41% showing no statistical significance in respect to great inter-animal variations.ConclusionThe application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances.Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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