title: The contribution of oxidative stress to drug-induced organ toxicity and its detection in vitro and in vivo.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pfizer R&D, Compound Safety Prediction-WWMC, Cell Based Assays and Mitochondrial Biology, Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Pereira
authors.forename: Sashi
authors.initials: S
authors.lastname: Nadanaciva
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Will
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species