The contribution of oxidative stress to drug-induced organ toxicity and its detection in vitro and in vivo

Expert Opin Drug Metab Toxicol. 2012 Feb;8(2):219-37. doi: 10.1517/17425255.2012.645536. Epub 2012 Jan 17.

Abstract

Introduction: Nowadays the 'redox hypothesis' is based on the fact that thiol/disulfide couples such as glutathione (GSH/GSSG), cysteine (Cys/CySS) and thioredoxin ((Trx-(SH)2/Trx-SS)) are functionally organized in redox circuits controlled by glutathione pools, thioredoxins and other control nodes, and they are not in equilibrium relative to each other. Although ROS can be important intermediates of cellular signaling pathways, disturbances in the normal cellular redox can result in widespread damage to several cell components. Moreover, oxidative stress has been linked to a variety of age-related diseases. In recent years, oxidative stress has also been identified to contribute to drug-induced liver, heart, renal and brain toxicity.

Areas covered: This review provides an overview of current in vitro and in vivo methods that can be deployed throughout the drug discovery process. In addition, animal models and noninvasive biomarkers are described.

Expert opinion: Reducing post-market drug withdrawals is essential for all pharmaceutical companies in a time of increased patient welfare and tight budgets. Predictive screens positioned early in the drug discovery process will help to reduce such liabilities. Although new and more efficient assays and models are being developed, the hunt for biomarkers and noninvasive techniques is still in progress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Brain / drug effects*
  • Chemical and Drug Induced Liver Injury / etiology*
  • Heart / drug effects*
  • Humans
  • Kidney / drug effects*
  • Mitochondria / metabolism
  • Models, Animal
  • Oxidative Stress*
  • Proteomics
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species