Nitro-L-arginine methyl ester: A potential protector against gentamicin ototoxicity

Conclusion The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this. Objective Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. Material and methods In this experimental study we used 30 Sprague–Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. Results L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

[1]  M. Takumida,et al.  Detection of nitric oxide in the guinea pig inner ear, using a combination of aldehyde fixative and 4,5-diaminofluorescein diacetate. , 2001 .

[2]  M. Anniko Nitric Oxide in Guinea Pig Vestibular Sensory Cells Following Gentamicin Exposure In Vitro , 2001, Acta oto-laryngologica.

[3]  M. Takumida,et al.  Pharmacological models for inner ear therapy with emphasis on nitric oxide. , 2001, Acta oto-laryngologica.

[4]  T. Nakashima,et al.  Vestibular and cochlear toxicity of aminoglycosides--a review. , 2000, Acta oto-laryngologica.

[5]  J. Thomsen,et al.  Preliminary results of a new delivery system for gentamicin to the inner ear in patients with Meniere’s disease , 2000, European Archives of Oto-Rhino-Laryngology.

[6]  P. Ernfors,et al.  Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  R. Popa Otoprotectant Minimizes Hearing Defects Caused by Pseudomonas aeruginosa Exotoxin A , 2000, Acta oto-laryngologica.

[8]  B. Conlon Topical Aminoglycoside Ototoxicity: Attempting to Protect the Cochlea , 2000, Acta oto-laryngologica.

[9]  F. Linthicum,et al.  Extraneous round Window Membranes and Plugs: Possible Effect on Intratympanic Therapy , 2000, The Annals of otology, rhinology, and laryngology.

[10]  M. Hoffer,et al.  A Radical Demise: Toxins and Trauma Share Common Pathways in Hair Cell Death , 1999, Annals of the New York Academy of Sciences.

[11]  J. Schacht,et al.  Stimulation of free radical formation by aminoglycoside antibiotics 1 The data in this paper have been presented, in part, at the meeting of the Association for Research in Otolaryngology, February 1996. 1 , 1999, Hearing Research.

[12]  J. Schacht,et al.  Iron chelators protect from aminoglycoside-induced cochleo- and vestibulo-toxicity. , 1998, Free radical biology & medicine.

[13]  Marcus Müller,et al.  Hair cell regeneration after local application of gentamicin at the round window of the cochlea in the pigeon , 1998, Hearing Research.

[14]  J. Schacht Aminoglycoside Ototoxicity: Prevention in Sight? , 1998, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[15]  Shinn Jb,et al.  Ear drop ototoxicity: reality or myth? , 1997 .

[16]  Marcos V. Goycoolea,et al.  Round window membrane. Structure function and permeability: A review , 1997, Microscopy research and technique.

[17]  M. F. Smith,et al.  Ear drop ototoxicity: reality or myth? , 1997, The American journal of otology.

[18]  T. Beveridge,et al.  Surface action of gentamicin on Pseudomonas aeruginosa , 1993, Journal of bacteriology.

[19]  M. Tateyama,et al.  [Aminoglycoside antibiotics]. , 1990, Nihon rinsho. Japanese journal of clinical medicine.

[20]  G. Rebillard,et al.  Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic conditions occurring in ageing. , 1990, Acta oto-laryngologica. Supplementum.