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Cited by 157Hearing, Cochlea, Tinnitus, GeneticsChemotherapy-induced organ toxicity mitigationVestibular and auditory disorders

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Variable efficacy of radical scavengers and iron chelators to attenuate gentamicin ototoxicity in guinea pig in vivo

Song, Ben-Bo, Schacht, Jochen·1996·Hearing Research
DOI 10.1016/0378-5955(96)00003-2
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Abstract

Recent studies from our laboratory have suggested that the ototoxic side effects of gentamicin are caused by a metabolized or 'activated' from the drug. Furthermore, we have postulated that the activation proceeds via the formation of an iron-gentamicin complex and that this complex produces free radicals. The present study assessed the protection effects of free radical scavengers and iron chelators on gentamicin-induced ototoxicity in guinea pigs in vivo. Gentamicin (120 mg/kg per day for 19 days) caused progressive threshold shifts reaching 50-65 dB at 18 kHz. Co-therapy with different radical scavengers yielded results ranging from no protection (with allopurinol, dimethyl sulfoxide, benzoate, lazaroid U74389G) to a moderate attenuation of hearing loss (with mannitol, 4-methylthiobenzoate, WR-2721). This finding agrees well with previous reports of inconsistent effects of scavengers on aminoglycoside-induced ototoxicity although it should be cautioned that only a single dose and route of application was tested. Two iron chelators, deferoxamine and 2,3-dihydroxybenzoate, significantly reduced the gentamicin-induced threshold shifts to about 10 dB or less. Iron chelators markedly decreased total serum iron levels while gentamicin treatment alone had no influence. There were no differences in serum gentamicin levels among all treated groups. This study confirms that iron plays a critical role in gentamicin ototoxicity and suggests that iron chelators, which are well-established drugs in clinical therapy, may be promising therapeutic agents to reduce aminoglycoside ototoxicity.

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Research works printed but not linked: 2

  1. Evenson, 1995, MTBA as a protective agent for cisplatin ototoxicity, Abstr. Assoc. Res. Otolaryngol., 18, 81
  2. Wang, 1996, The iron embrace: exposing the secret activities of gentamicin, Abst. Assoc. Res. Otolaryngol., 19, 29

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Metadata

Authors
Song, B.-B., & Schacht, J.
Affiliations
University of Michigan (US)
Corresponding author
Schacht, Jochen
ORCID
Schacht, Jochen
Venue
Hearing Research
Publisher
Elsevier BV
Published
1996-05
Volume
94
Issue
1-2
Pages
87-93
ISSN
0378-5955 (ISSN-L)
DOI
10.1016/0378-5955(96)00003-2
OpenAlex
W2047770131
Cited by
157
References
41
Citations by year
2026: 1 · 2024: 6 · 2023: 1 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 6
FWCI
7.97
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Hearing Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Deafness and Other Communication Disorders (DC-00124)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Chemotherapy-induced organ toxicity mitigation
  • Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
Keywords
gentamicin ototoxicity, aminoglycoside ototoxicity, radical scavengers, iron chelators, threshold shift, deferoxamine, 2,3-dihydroxybenzoate, serum iron, guinea pig
MeSH terms
Administration, Oral, Allopurinol, Analysis of Variance, Animals, Anti-Bacterial Agents, Antimetabolites, Antioxidants, Auditory Threshold, Benzoates, Deferoxamine, Dimethyl Sulfoxide, Amifostine, Gentamicins, Guinea Pigs, Injections, Intraperitoneal, Injections, Subcutaneous, Iron, Iron Chelating Agents, Male, Mannitol, Pregnatrienes, Free Radical Scavengers, Hydroxybenzoates

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