The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig In Vivo,
Abstract
This study details the prevention of gentamicin-induced hearing loss in guinea pig in vivo. The approach is based on our recent demonstrations of a redox-active gentamicin-iron complex in vitro and partial attenuation of gentamicin-induced hearing loss by the iron chelators deferoxamine and 2,3-dihydroxybenzoate. In our study, guinea pigs receiving injections of gentamicin (120 mg/kg body weight daily x 19 days) developed a progressive threshold shift reaching 50 to 70 dB at 18 kHz. Concurrent treatment with different doses of 2,3-dihydroxybenzoate (30-300 mg/kg/day) reduced the threshold shift to 25 to 15 dB. Coinjection of gentamicin with dihydroxybenzoate (100 mg/kg/day) plus mannitol (15 mg/kg/day) yielded complete functional and morphological protection from gentamicin ototoxicity although partial protection was observed with combinations of dihydroxybenzoate and deferoxamine. Dihydroxybenzoate also attenuated gentamicin-induced vestibular toxicity. The iron chelators and radical scavengers affected neither serum levels nor the antimicrobial efficacy of gentamicin against Escherichia coli. These results confirm that iron and free radicals play a crucial role in the toxic side effects of gentamicin. Furthermore, they suggest that iron chelators, which are well-established drugs in clinical therapy, may be promising therapeutic agents to reduce aminoglycoside ototoxicity.
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“Thus, gentamicin can form a gentamicin-iron complex that can lead to toxic symptoms such as hearing loss; this is reversed by iron chelators [1788,1789].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1788]
Citations
Cites
Gutteridge, J. M. C., Richmond, R., & Halliwell, B. B. (1979) · Biochemical Journal · doi:10.1042/bj1840469 · Cited by 624
A suggested approach to once‐daily aminoglycoside dosing.
Begg, E., Barclay, M. L., & Duffull, S. B. (1995) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1995.tb05719.x · Cited by 424
Starke-Reed, P. E., & Farber, J. L. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39218-9 · Cited by 298
Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats.
Walker, P. D., & Shah, S. V. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113325 · Cited by 298
Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex
Priuska, E. M., & Schacht, J. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)02160-4 · Cited by 287
Self-citationGentamicin nephrotoxicity in humans and animals: Some recent research
Ali, B. H. (1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)00049-6 · Cited by 183
Song, B.-B., & Schacht, J. (1996) · Hearing Research · doi:10.1016/0378-5955(96)00003-2 · Cited by 157
Self-citationAttenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo
Garetz, S. L., Altschuler, R. A., & Schacht, J. (1994) · Hearing Research · doi:10.1016/0378-5955(94)90255-0 · Cited by 142
Self-citationScar formation after drug-induced cochlear insult
Raphael, Y., & Altschuler, R. A. (1991) · Hearing Research · doi:10.1016/0378-5955(91)90034-7 · Cited by 132
Biochemical Basis of Aminoglycoside Ototoxicity
Schacht, J. (1993) · Otolaryngologic Clinics of North America · doi:10.1016/s0030-6665(20)30771-4 · Cited by 125
Self-citation
Research works printed but not linked: 3
- Martini, 1952, Pharmacology of 2,3-dihydroxybenzoic acid., Arch. Ital. Sci. Farmacol., 2, 259
- Sha, 1996, Amplification of free radicals by gentamicin in a biological system (Abstract)., Abs. Assoc. Res. Otolaryngol., 19, 30
- Wang, 1996, The iron embrace: exposing the secret activities of gentamicin (Abstract)., Abs. Assoc. Res. Otolaryngol., 19, 29
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Aminoglycosides: Nephrotoxicity
Mingeot‐Leclercq, M., & Tulkens, P. M. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.5.1003 · Cited by 759
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Sha, S., Taylor, R., Forge, A., & Schacht, J. (2001) · Hearing Research · doi:10.1016/s0378-5955(01)00224-6 · Cited by 408
Self-citationAminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague–Dawley rat
Wu, W.-J., Sha, S., McLaren, J. D., Kawamoto, K., Raphael, Y., & Schacht, J. (2001) · Hearing Research · doi:10.1016/s0378-5955(01)00303-3 · Cited by 226
Self-citationSha, S., & Schacht, J. (2000) · Hearing Research · doi:10.1016/s0378-5955(00)00003-4 · Cited by 222
Self-citation
Metadata
- Authors
- Song, B.-B., Anderson, D. J., & Schacht, J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Schacht, Jochen
- ORCID
- Schacht, Jochen
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1997-07
- Volume
- 282
- Issue
- 1
- Pages
- 369-377
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1916770705
- Cited by
- 111
- References
- 37
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- 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, iron chelators, 2,3-dihydroxybenzoate, deferoxamine, free radicals, hearing threshold shift, vestibular toxicity, radical scavengers, mannitol, guinea pig, drug-induced hearing loss
- MeSH terms
- Animals, Anti-Bacterial Agents, Gentamicins, Guinea Pigs, Hearing Disorders, Iron, Iron Chelating Agents, Male, Serum Albumin, Weight Gain, Evoked Potentials, Auditory, Brain Stem, Nystagmus, Optokinetic
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