[Iron chelation. Biological significance and medical application]. / Eisenchelierung. Biologische Bedeutung und medizinische Anwendungen.

ABSTRACT

Iron, an essential element for all aerobic organisms, exists in a very insoluble form under physiological conditions. Therefore, most microorganisms secrete iron chelating compounds called siderophores which are able to sequester ferric ions from the environment. A vast number of such compounds has been isolated from cultures of microorganisms and tested for enhancement of iron excretion in experimental animals. Only one compound, deferrioxamine B, has been shown to be clinically effective and well tolerated in humans suffering from chronic iron overload. However, this drug can only be administered successfully by injection or slow infusion. In spite of considerable research it has not been possible to overcome this drawback by developing suitable formulations or derivatives which are orally active. Deferri-ferrithiocin, a novel type of siderophore, has recently been isolated from a streptomyces culture. This substance is well absorbed orally and has been shown to enhance the excretion of ferric ion in iron loaded rats. Further investigations are now necessary to establish acute toxicity levels and longterm tolerability before efficacy tests in man can be planned. Other recent developments in the field of metal chelation include experimental studies using deferrioxamine for the treatment of conditions resulting from toxic levels of iron or aluminium in chronically dialyzed patients. In addition, attempts are being made to administer chelation therapy in the treatment of various infections and chronic inflammation, as well as other conditions linked with disorders of iron metabolism.