Expert opinion on investigational drugs · 2013
Potential clinical applications of chelating drugs in diseases targeting transferrin-bound iron and other metals.
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Kontoghiorghe Christina N, Kolnagou Annita, Kontoghiorghes George J
Аннотация
INTRODUCTION: Iron is essential for normal, neoplasmic and microbial cells. Transferrin (Tf) is responsible for iron transport and its interactions with chelators are of physiological and toxicological importance and could lead to new therapeutic applications.
AREAS COVERED: Differential interactions of Tf with chelators such as deferiprone (L1) could be used to modify toxicity and disease pathways in relation to iron and other metal metabolism. Iron mobilization by L1 could achieve normal body iron stores in thalassemia patients. Iron mobilization from the reticuloendothelial system by L1 and exchange with Tf could be used to increase the production of hemoglobin in the anemia of chronic disease. Iron accumulation is pathogenic in neurodegenerative, acute kidney and other diseases and could be removed by L1 with therapeutic implications. Deprivation of iron from neoplasmic and microbial cells by chelators could increase the prospect of improved treatments in cancer and infectious diseases. Other applications include metal detoxification and inhibition of oxidative stress-related conditions.
EXPERT OPINION: Specific mechanisms apply in the interactions of chelators with Tf, which could be used in the design of targeted therapeutic strategies in many conditions. In each case specific chelator protocols have to be designed for achieving optimum therapeutic activity.
AREAS COVERED: Differential interactions of Tf with chelators such as deferiprone (L1) could be used to modify toxicity and disease pathways in relation to iron and other metal metabolism. Iron mobilization by L1 could achieve normal body iron stores in thalassemia patients. Iron mobilization from the reticuloendothelial system by L1 and exchange with Tf could be used to increase the production of hemoglobin in the anemia of chronic disease. Iron accumulation is pathogenic in neurodegenerative, acute kidney and other diseases and could be removed by L1 with therapeutic implications. Deprivation of iron from neoplasmic and microbial cells by chelators could increase the prospect of improved treatments in cancer and infectious diseases. Other applications include metal detoxification and inhibition of oxidative stress-related conditions.
EXPERT OPINION: Specific mechanisms apply in the interactions of chelators with Tf, which could be used in the design of targeted therapeutic strategies in many conditions. In each case specific chelator protocols have to be designed for achieving optimum therapeutic activity.