Risk/benefit assessment, advantages over other drugs and targeting methods in the use of deferiprone as a pharmaceutical antioxidant in iron loading and non iron loading conditions

Abstract

Tissue damage caused by oxidative stress is a common characteristic of many conditions involving different major organs such as the brain, heart, liver and kidneys. The treatment of such conditions using classical antioxidants is not in most cases sufficient or effective because it lacks specificity and has a low therapeutic index. Increased evidence from in vitro, in vivo and clinical studies suggest that deferiprone (L1) can be used as a potent pharmaceutical antioxidant by mobilizing labile iron and copper and/or inhibiting their catalytic activity in the formation of free radicals and oxidative stress in tissue damage. The high therapeutic index, tissue penetration, rapid iron binding and clearance of the iron complex, and the low toxicity of L1, support its application as an antioxidant pharmaceutical for adjuvant, alternative or main therapy, especially in conditions where other treatments have failed. Substantial clinical improvement and reversal in most cases of the tissue damage has been observed in cardiomyopathy in thalassemia, diabetic nephropathy and glomerulonephritis in kidney disease, Friedreich's Ataxia and Fanconi Anemia patients. In contrast to L1, both deferoxamine (DFO) and deferasirox (DFRA) have major disadvantages in their use in non iron loading conditions due to toxicity implications. Further studies in the above and other conditions and optimization of the L1 therapy in each individual will increase the prospects of the application and role of L1 as a universal antioxidant pharmaceutical.