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Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
2005 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 125, no 10, 1033-8 p.Article in journal (Refereed) Published
Abstract [en]

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.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. 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. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.

Place, publisher, year, edition, pages
2005. Vol. 125, no 10, 1033-8 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89799DOI: 10.1080/00016480510038022PubMedID: 16298782OAI: oai:DiVA.org:uu-89799DiVA: diva2:161563
Available from: 2002-04-10 Created: 2002-04-10 Last updated: 2010-03-03Bibliographically approved
In thesis
1. The Round Window Membrane - Gateway to the Cochlea: A Morphological and Electrophysiological study
Open this publication in new window or tab >>The Round Window Membrane - Gateway to the Cochlea: A Morphological and Electrophysiological study
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Topical treatment of several inner ear diseases through the round window membrane (RWM) might be feasible in the near future. Bacteria toxins, ototoxic drugs and noise trauma seem to harm the inner ear by a common pathway which involves, excessive outflow of the afferent neurotransmitter glutamate and formation of nitric oxide (NO), which can severely damage cells/nerve endings and lead to cell death.

In this study we used 98 Sprague-Dawley rats and seven human temporal bones. Various substances were instilled into the middle ear of the rat, such as Pseudomonas Aeruginosa Exotoxin (PaExoA), gentamicin, NO-inhibitor N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME), and glucocorticoids. The effects of the substances were studied by morphological analysis of RWM and the endolymphatic sac (ES) by light and electron microscopic. Hearing level was measured in the rats by ABR technique. The human temporal bones were studied immunomorphologically to search for glutamate.

In the human inner ear, glutamate receptors and glutamine synthetase, were identified. In the rat, we found, following PaExoA exposure, reversible and permanent hearing loss and morphological changes in the RWM. The ES showed increased numbers of macrophages and thickening of the epithelia. When L-NAME was used as an otoprotector from gentamicin ototoxicity a therapeutic effect in the high frequency area was found. Hydrocortisone (but not dexamethasone) exposure of the RWM resulted in membrane thickening, and adjacent to the membrane, inflammatory cells.

The importance of the RWM as a portal for toxic substances and topical treatment of inner ear diseases was highlighted in this study. The difficulties of applying drugs in the round window niche were exposed. The results of this study add important knowledge concerning certain mechanisms of inner ear injury and help us to understand possibilities and problems of local treatment of inner ear diseases in patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 33 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1134
Otorhinolaryngology, round window membrane, pseudomonas exotoxin, auditory brainstem response, hearing loss, endolymphatic sac, inner ear immunology, glutamate, nitric oxide inhibitor, glucocorticoid., Otorhinolaryngologi
National Category
Research subject
urn:nbn:se:uu:diva-1969 (URN)91-554-5277-9 (ISBN)
Public defence
2002-05-03, Skoogsalen, ingång 78/79, 1 trappa, Uppsala, 13:15
Available from: 2002-04-10 Created: 2002-04-10Bibliographically approved

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