抗氧化剂的药理应用：阳面与阴面

Title:Pharmacological Applications of Antioxidants: Lights and Shadows

Volume: 15 Issue: 13

Author(s): Luciano Saso and Omidreza Firuzi

Affiliation:

关键词: 抗氧化剂，线粒体功能障碍，神经退行性疾病，Nrf2，NOX

摘要: Oxidative stress is linked with many pathologies ranging from cancer to neurodegenerative disorders and antioxidants have presumably therapeutic value in such diseases. In this review, we categorize different direct and indirect mechanisms by which antioxidants exert their action. These include scavenging and metal chelating effects, mimicking the antioxidant enzymes or upregulation of their expression, activation of nuclear factor erythroid 2-related factor 2 (Nrf2), increasing the activity of sirtuins and inhibition of pro-oxidant enzymes among others. Recent findings on the most frequently investigated antioxidants including polyphenolics, thiolics, spin trapping agents, SOD mimetics, inducers of heme oxygenase-1 and nitric oxide synthase, activators of Nrf2, NADPH oxidase inhibitors and herbal supplements are summarized. Furthermore, the antioxidant effects of drugs that are clinically used for other pharmacological purposes including ACE inhibitors and statins are discussed. Cost-effectiveness and adverse effects of antioxidants are also evaluated. Since antioxidant therapy has failed in many instances, we have classified the reasons that may explain these shortcomings in different categories. Novel approaches to antioxidant therapy, that include mitochondria-targeting drugs, antioxidant gene therapy and approaches for improvement of cell uptake and alteration of subcellular compartment localization are also described. In the end, “shadows” that are shortcomings of antioxidant therapy as well as “lights” that include positive outcomes are addressed. It is concluded that if we learn from failures, invest on agents with higher potential and take advantage of novel emerging approaches, antioxidants could be an asset for the management of certain carefully chosen oxidative stress-related diseases.

Cite this article as:

Luciano Saso and Firuzi Omidreza, Pharmacological Applications of Antioxidants: Lights and Shadows, Current Drug Targets 2014; 15 (13) . https://dx.doi.org/10.2174/1389450115666141024113925