Prospects for introducing deferiprone as potent pharmaceutical antioxidant.
Free radical formation is primarily initiated from metal catalytic centers involving iron and copper. Under certain conditions, free radical reactions can lead to free radical cascades and oxidative stress, which can cause biomolecular, cellular and tissue damage (FRD). The use of natural antioxidants to prevent FRD is in most cases not effective. Many chelators have been shown to inhibit free radical reactions and toxicity in experimental models of both in vitro and in vivo. Deferiprone (L1) has been shown to be effective and safe in the reversal of accelerating oxidative stress related tissue damage in iron loading and non iron loading conditions such as cardiomyopathy in thalassaemia, acute kidney disease and Friedreich ataxia. The selection of chelating drugs and their combinations could be used as new strategies for antioxidant therapies. In vitro, in vivo and clinical data suggest that L1 is the most potent drug antioxidant because of its high therapeutic index, ability to reach extracellular and intracellular compartments of many tissues and ability to inhibit both iron and copper catalysed free radical reactions.
Kontoghiorghes
George J
GJ
Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus. kontoghiorghes.g.j@pri.ac.cy
D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D015913:Chelation Therapy / Q000379:methods*; D003300:Copper / Q000378:metabolism; D000077543:Deferiprone; D055808:Drug Discovery; D005609:Free Radicals / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism*; D011728:Pyridones / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity
D000975:Antioxidants; D005609:Free Radicals; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003300:Copper; D007501:Iron