title: Fungal siderophores function as protective agents of LDL oxidation and are promising anti-atherosclerotic metabolites in functional food.
abstract: Iron-mediated oxidation of low-density lipoprotein has been implicated in the pathogenesis of vascular disorders such as atherosclerosis. The present investigations were performed to test whether hydrophobic fungal siderophores - hexadentate trihydroxamates desferricoprogen, desferrichrome, desferrirubin, and desferrichrysin - might suppress heme-catalyzed LDL oxidation and the toxic effects of heme-treated LDL on vascular endothelium. Indeed, two of these - desferricoprogen and desferrichrome - markedly increased the resistance of LDL to heme-catalyzed oxidation. In similar dose-response fashion, these siderophores also inhibited the generation of LDL products cytotoxic to human vascular endothelium. When iron-free fungal siderophores were added to LDL/heme oxidation reactions, the product failed to induce heme oxygenase-1, a surrogate marker for the noncytocidal effects of oxidized LDL (not in the case of desferrichrysin). Desferricoprogen also hindered the iron-mediated peroxidation of lipids from human atherosclerotic soft plaques in vitro, and was taken up in the gastrointestinal tract of rat. The absorbed siderophore was accumulated in the liver and was secreted in its iron-complexed form in the feces and urine. The consumption of mold-ripened food products such as aged cheeses and the introduction of functional foods and food additives rich in fungal iron chelators in diets may lower the risk of cardiovascular diseases.
authors.affiliation: Department of Microbial Biotechnology and Cell Biology, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Pócsi
authors.forename: Viktória
authors.initials: V
authors.lastname: Jeney
authors.forename: Pál
authors.initials: P
authors.lastname: Kertai
authors.forename: Imre
authors.initials: I
authors.lastname: Pócsi
authors.forename: Tamás
authors.initials: T
authors.lastname: Emri
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Gyémánt
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
authors.forename: József
authors.initials: J
authors.lastname: Balla
authors.forename: György
authors.initials: G
authors.lastname: Balla
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D054659:Diketopiperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017262:Siderophores / Q000494:pharmacology*
chemical_list: D054659:Diketopiperazines; D006877:Hydroxamic Acids; D007502:Iron Chelating Agents; D008077:Lipoproteins, LDL; D020011:Protective Agents; D017262:Siderophores; C099252:oxidized low density lipoprotein; C010896:coprogen; D051547:Heme Oxygenase-1; C047664:desferricoprogen