title: In vitro heme and non-heme iron capture from hemoglobin, myoglobin and ferritin by bovine lactoferrin and implications for suppression of reactive oxygen species in vivo.
abstract: Lactoferrin (Lf), present in colostrum and milk is a member of the transferrin family of iron-binding glyco-proteins, with stronger binding capacity to ferric iron than hemoglobin, myoglobin or transferrin. Unlike hemoglobin and myoglobin, iron-bound Lf is reasonably stable to gastric and duodenal digestive conditions. Unlike ferrous iron, ferric iron is not directly reactive with oxygen supporting the capacity of Lf capture of heme iron to suppress reactive oxygen species (ROS) production. We therefore hypothesized that bovine Lf could capture and thereby terminate the cycle of ROS production by heme iron. The transfer of heme iron from either intact or digested forms of hemoglobin and myoglobin and from intact ferritin was demonstrated by in vitro methods, monitoring Fe-saturation status of Lf by changes in absorptivity at 465 nm. The results are discussed in the context of new proposed opportunities for orally administered Lf to regulate oxidative damage associated with heme iron. In addition to potentially suppressing oxidative heme-iron-mediated tissue damage in the lumen, Lf is expected to also reverse the overload of ferritin-bound iron, that accompanies chronic inflammation and aging. These new proposed uses of Lf are additional to known host defense functions that include anti-microbial, anti-viral properties, immune and cancer cell growth regulation. The findings and interpretations presented require clinical substantiation and may support important additional protective and therapeutic uses for Lf in the future.
authors.affiliation: CSIRO Food, Nutrition and Bioproducts, Private Bag 16, 671 Sneydes Road, Werribee, VIC, 3030, Australia.
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Jegasothy
authors.forename: Rangika
authors.initials: R
authors.lastname: Weerakkody
authors.forename: Sophie
authors.initials: S
authors.lastname: Selby-Pham
authors.forename: Louise E
authors.initials: LE
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002712:Chlorides / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005290:Ferric Compounds / Q000378:metabolism; D005293:Ferritins / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D019266:Iron, Dietary; D007781:Lactoferrin / Q000378:metabolism*; D008954:Models, Biological; D009211:Myoglobin / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D006454:Hemoglobins; D019266:Iron, Dietary; D009211:Myoglobin; D017382:Reactive Oxygen Species; D006418:Heme; D005293:Ferritins; D007501:Iron; D007781:Lactoferrin; C024555:ferric chloride