Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherTOXICOLOGY

Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig In Vivo ,

Ben-Bo Song, David J. Anderson and Jochen Schacht
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 369-377;
Ben-Bo Song
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David J. Anderson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jochen Schacht
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

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 × 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.

Footnotes

  • Send reprint requests to: Dr. Jochen Schacht, Kresge Hearing Research Institute, 1301 East Ann Street, Ann Arbor, MI 48109-0506.

  • ↵1 This work was supported by research Grant DC-00124 from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health.

  • ↵2 A preliminary report was presented at the 19th Midwinter Meeting of the Association for Research in Otolaryngology, St. Petersburg Beach, FL, February, 1996.

  • Abbreviations:
    ABR
    auditory brainstem responses
    DHB
    2,3-dihydroxybenzoic acid
    DFO
    deferoxamine mesylate
    GM
    gentamicin
    GSH
    glutathione
    MANN
    mannitol
    OHC
    outer hair cell
    PBS
    phosphate-buffered saline
    • Received September 30, 1996.
    • Accepted March 17, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig In Vivo ,
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherTOXICOLOGY

Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig In Vivo ,

Ben-Bo Song, David J. Anderson and Jochen Schacht
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 369-377;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherTOXICOLOGY

Protection from Gentamicin Ototoxicity by Iron Chelators in Guinea Pig In Vivo ,

Ben-Bo Song, David J. Anderson and Jochen Schacht
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 369-377;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Nafamostat is a Potent Human Diamine Oxidase Inhibitor
  • Chemoproteomics Investigation of Testicular Toxicity with BTK Inhibitor
  • Bosentan Alters Bile Salt Disposition
Show more Toxicology

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics