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

• Published in: Nature reviews. Drug discovery Vol. 20; no. 9; pp. 689 - 709
• Main Authors: Forman, Henry Jay, Zhang, Hongqiao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2021; Nature Publishing Group
• Subjects: 631/154; 631/45; Alzheimer's disease; Animals; Antioxidants; Antioxidants - pharmacology; Atherosclerosis; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer; Cancer Research; Cardiovascular diseases; Chronic obstructive pulmonary disease; Clinical trials; Development and progression; Disease prevention; Drug Development; Drug Evaluation, Preclinical; Drug therapy; Enzymes; Health aspects; Humans; Lipids; Lung diseases; Medicinal Chemistry; Molecular Medicine; Molecular Targeted Therapy; Oxidation; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Pathology; Pharmacology/Toxicology; Physiological aspects; Physiology; Review; Review Article; Signal transduction; Signal Transduction - drug effects; Transcription factors; United States
• ISSN: 1474-1776; 1474-1784; 1474-1784
• DOI: 10.1038/s41573-021-00233-1

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. Although oxidative stress is associated with a broad range of diseases, therapeutic antioxidant approaches have so far been disappointing. Here, Forman and Zhang review the roles of oxidative stress and redox signalling in disease, assess antioxidant therapeutic strategies and highlight key limitations that have challenged their clinical application.