title: Doxycycline reduces nitric oxide production in guinea pig inner ears.
abstract: OBJECTIVE
  Gentamicin 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The application of doxycycline might offer a new therapeutic approach to prevent NO-induced cochlea damage through ototoxic substances.
authors: 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
authors: Kai
authors: K
authors: Helling
authors: Karl
authors: K
authors: Wodarzcyk
authors: Jürgen
authors: J
authors: Brieger
authors: Irene
authors: I
authors: Schmidtmann
authors: Huige
authors: H
authors: Li
authors: Wolf J
authors: WJ
authors: Mann
authors: Ulf-Rüdiger
authors: UR
authors: Heinrich