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Protective effect of edaravone against tobramycin-induced 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, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
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2009 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 129, no 1, 8-13 p.Article in journal (Refereed) Published
Abstract [en]

CONCLUSION: It is suggested that simultaneous treatment with the radical scavenger edaravone has an effective protective effect against tobramycin ototoxicity in rat. Even if the edaravone treatment is postponed for 7 days, it can still prevent hearing loss, but a 14 day delay cannot protect from ototoxicity. OBJECTIVES: With the aim of alleviating hearing loss caused by aminoglycoside ototoxicity, we performed a trial to assess the hearing protective efficacy of the radical scavenger edaravone. MATERIALS AND METHODS: In part one of the study, 21 male Sprague-Dawley albino rats were used; 2 rats served as controls for the safety of edaravone. Eight rats each received 10 subcutaneous injections (s.c.) of tobramycin (160 mg/kg b.w.) once daily and saline injection intraperitoneally for 2 weeks. Eleven rats were given 10 s.c. tobramycin injections simultaneously with an intraperitoneal injection of edaravone (3 mg/kg b.w.). In part two, tobramycin was injected in 13 rats (as above). Five of these received two edaravone injections 7 days later and four rats similarly 14 days later. Auditory brainstem response (ABR) was used to assess hearing. RESULTS: All rats treated only with tobramycin showed a deterioration of hearing. None of the rats given simultaneous treatment with tobramycin and edaravone demonstrated hearing loss. A 7 day delay in edaravone injection still prevented hearing loss, but a 14 day delay had only a temporary prophylactic effect.

Place, publisher, year, edition, pages
2009. Vol. 129, no 1, 8-13 p.
Keyword [en]
Animal, rat, auditory brainstem response, edaravone, aminogycoside, hearing loss, cochlear ototoxicity, cochlear protection, reactive oxygen species, antioxidant
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-113361DOI: 10.1080/00016480802008199ISI: 000261847700002PubMedID: 18607936OAI: oai:DiVA.org:uu-113361DiVA: diva2:290593
Available from: 2010-01-27 Created: 2010-01-27 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Time-related Aspects of Otoprotection: Experimental Studies in Rat
Open this publication in new window or tab >>Time-related Aspects of Otoprotection: Experimental Studies in Rat
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Intratympanic injection of various otoprotectants through the round window membrane (RWM) might become available in the near future as an alternative to the currently available medical and surgical methods used to treat several inner ear diseases. The most common outcome of such diseases is sensorineural hearing loss (SNHL).

Two examples of  these otoprotectants are Edaravone and Brain-Derived Neurotrophic Factor (BDNF), both of which have already proved effective against  noise-induced hair cell loss, barotrauma  and ototoxicity caused by cisplatin. In four different studies we used two electrophysiological methods, auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), to study the effects of tobramycin and Pseudomonas aeruginosa exotoxin A (PaExoA) on the inner ears of 129 male Sprague-Dawley rats.

In two investigations, not only the otoprotective effects of Edaravone on tobramycin-induced ABR threshold shifts and PaExoA-induced DPOAE  threshold changes, were studied but even different application times, in order to establish in which interval it was still possible to achieve effective otoprotection.We found that Edaravone gave otoprotection from tobramycin when injected simultaneously or within 7 days, but it had only a limited effect on the changes in DPOAE thresholds caused by PaExoA when injected 1, 2, or 4 hours after the exotoxin.

The effect of BDNF on PaExoA-induced ABR threshold shifts was investigated in two studies, where different doses of intratympanically injected PaExoA were used and where BDNF was applied simultaneously, 12 or 72 hours efter exotoxin instillation. We found that BDNF had an otoprotective effect on SNHL induced by different doses PaExoA when injected simultaneously or with no more than 12 hours delay.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 901
Keyword
sensorineural hearing loss, Edaravone, brain-derived neurotrophic factor, auditory brainstem response, Sprague-Dawley rat, distortion product otoacoustic emission, Pseudomonas aeruginosa exotoxin A.
National Category
Medical and Health Sciences
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:uu:diva-198450 (URN)978-91-554-8661-7 (ISBN)
Public defence
2013-06-13, Skoogsalen, Akademiska sjukhuset (ingång 78-79), Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-05-22 Created: 2013-04-15 Last updated: 2013-08-30

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Stenkvist Asplund, MonikaLidian, AdnanLinder, BirgittaAnniko, Matti

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