Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Nat Rev Drug Discov. 2021 Sep;20(9):689-709. doi: 10.1038/s41573-021-00233-1. Epub 2021 Jun 30.

Abstract

Oxidative stress is a component of many diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer disease and cancer. Although numerous small molecules evaluated as antioxidants have exhibited therapeutic potential in preclinical studies, clinical trial results have been disappointing. A greater understanding of the mechanisms through which antioxidants act and where and when they are effective may provide a rational approach that leads to greater pharmacological success. Here, we review the relationships between oxidative stress, redox signalling and disease, the mechanisms through which oxidative stress can contribute to pathology, how antioxidant defences work, what limits their effectiveness and how antioxidant defences can be increased through physiological signalling, dietary components and potential pharmaceutical intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Drug Development*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Targeted Therapy
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Signal Transduction / drug effects

Substances

  • Antioxidants