Prospects for the introduction of targeted antioxidant drugs for the prevention and treatment of diseases related to free radical pathology
George J Kontoghiorghes & Christina N Kontoghiorghe
Received 16 Feb 2019, Accepted 09 Jun 2019, Accepted author version posted online: 11 Jun 2019
Download citation https://doi.org/10.1080/13543784.2019.1631284
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Abstract
Introduction: Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target essential pathways of OST in many pathological conditions. The pharmacological parameters required by antioxidant drugs in relation to the OST target characteristics include the determination of the therapeutic index, ADMET and drug interactions. Antioxidant drug development efforts are currently targeting the treatment of severe diseases with no proven effective therapies.
Areas covered: This article addresses the damaging effects of oxidative stress toxicity, prospects for the development of pharmaceutical antioxidants and clinical studies using other drugs with antioxidant potential.
Expert opinion: Effective antioxidant therapeutic strategies should include the design of protocols for the inhibition of OST through iron chelation, administration of synthetic and natural antioxidants and enhancement of the antioxidant defences by increasing the production of endogenous antioxidants and activation of antioxidant mechanisms. Different therapeutic strategies apply in the use of antioxidant drugs for one or more targets, for prevention, treatment, or of post-treatment effects and for systematic, long-term or short-term applications. The design of new antioxidant drugs and effective protocols which can include Deferiprone and N-acetylcysteine combinations, could lead to the development of a new class of therapeutics for clinical use.
Keywords: iron, chelators, iron overload, non-iron loaded diseases, free radicals oxidative stress, thalassaemia, cancer, deferiprone, N-acetylcysteine
George J Kontoghiorghes & Christina N Kontoghiorghe
Received 16 Feb 2019, Accepted 09 Jun 2019, Accepted author version posted online: 11 Jun 2019
Download citation https://doi.org/10.1080/13543784.2019.1631284
Select Language▼
Translator disclaimer
Accepted author version
Abstract
Introduction: Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target essential pathways of OST in many pathological conditions. The pharmacological parameters required by antioxidant drugs in relation to the OST target characteristics include the determination of the therapeutic index, ADMET and drug interactions. Antioxidant drug development efforts are currently targeting the treatment of severe diseases with no proven effective therapies.
Areas covered: This article addresses the damaging effects of oxidative stress toxicity, prospects for the development of pharmaceutical antioxidants and clinical studies using other drugs with antioxidant potential.
Expert opinion: Effective antioxidant therapeutic strategies should include the design of protocols for the inhibition of OST through iron chelation, administration of synthetic and natural antioxidants and enhancement of the antioxidant defences by increasing the production of endogenous antioxidants and activation of antioxidant mechanisms. Different therapeutic strategies apply in the use of antioxidant drugs for one or more targets, for prevention, treatment, or of post-treatment effects and for systematic, long-term or short-term applications. The design of new antioxidant drugs and effective protocols which can include Deferiprone and N-acetylcysteine combinations, could lead to the development of a new class of therapeutics for clinical use.
Keywords: iron, chelators, iron overload, non-iron loaded diseases, free radicals oxidative stress, thalassaemia, cancer, deferiprone, N-acetylcysteine
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