Oxidative stress is linked with many pathologies ranging from cancer to neurodegenerative diseases and antioxidants are presumably of therapeutic value in such diseases. In this review, we categorize different direct and indirect mechanisms by which antioxidants exert their action, including 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 also 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 some of the carefully chosen oxidative stress-related diseases.

Pharmacological Applications of Antioxidants: Lights and Shadows / Saso, Luciano; O., Firuzi. - In: CURRENT DRUG TARGETS. - ISSN 1389-4501. - STAMPA. - (2014), pp. 1177-1199.

Pharmacological Applications of Antioxidants: Lights and Shadows.

SASO, Luciano;
2014

Abstract

Oxidative stress is linked with many pathologies ranging from cancer to neurodegenerative diseases and antioxidants are presumably of therapeutic value in such diseases. In this review, we categorize different direct and indirect mechanisms by which antioxidants exert their action, including 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 also 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 some of the carefully chosen oxidative stress-related diseases.
2014
01 Pubblicazione su rivista::01a Articolo in rivista
Pharmacological Applications of Antioxidants: Lights and Shadows / Saso, Luciano; O., Firuzi. - In: CURRENT DRUG TARGETS. - ISSN 1389-4501. - STAMPA. - (2014), pp. 1177-1199.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/645416
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