In vitro and in vivo models of drug ototoxicity: studying the mechanisms of a clinical problem

Expert Opin Drug Metab Toxicol. 2011 Dec;7(12):1521-34. doi: 10.1517/17425255.2011.614231. Epub 2011 Oct 14.

Abstract

Introduction: Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with narcotic medication. These medications are prescribed despite their side effects, which includes inner ear toxicity, because they are life-saving drugs or there is a lack of better treatment.

Areas covered: This review will discuss in vitro and in vivo models of ototoxicity highlighting recently published ototoxicity research. The reader will learn the strengths and limitations of different ototoxicity models and what molecular insights have been gained from their application. A better understanding of the cellular mechanisms of these ototoxins will help in the discovery of ways to prevent and treat hearing loss associated with ototoxic medications.

Expert opinion: There are benefits to both in vitro and in vivo models of ototoxicity. Research of a particular medication and its ototoxic mechanisms should draw from several models, enabling a better answer to the clinical question of prevention and treatment of inner ear drug toxicity.

Publication types

  • Review

MeSH terms

  • Acetaminophen / adverse effects
  • Aminoglycosides / adverse effects
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Antimalarials / adverse effects
  • Antineoplastic Agents / adverse effects
  • Cells, Cultured
  • Cisplatin / adverse effects
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions
  • Ear Diseases / chemically induced
  • Ear Diseases / pathology*
  • Ear Diseases / prevention & control
  • Ear, Inner / anatomy & histology
  • Ear, Inner / drug effects
  • Humans
  • Macrolides / adverse effects
  • Models, Animal

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimalarials
  • Antineoplastic Agents
  • Macrolides
  • Acetaminophen
  • Cisplatin