Targeting oxidative stress in disease: promise and limitations of antioxidant therapy
By H. Forman, Hongqiao Zhang. Nature reviews. Drug discovery, 2021
2,390 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Nutrition and Dietetics, Organic Chemistry
View Paper: https://www.semanticscholar.org/paper/abeb0a3504bb7142853f5105a1dc6177e6db8c2e
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Citations in the corpus
- Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances (2025, positive): “3,4 7 It also in fl uences pyroptosis through the mediation of NOD-like receptor and pyrin domain containing-3 (NLRP3) in fl ammasome in response to certain stimuli.”
- Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants (2024, background): “Although several authors (Forman and Zhang 2021) consider the synthesis of glutathione (GSH) and thioredoxin (Trx-Red or Trx-SH) to constitute the second line of antioxidant defense, we include these endogenous antioxidant molecules in the first line of antioxidant defense because they act as…”