title: Iron derivatives from casein hydrolysates as a potential source in the treatment of iron deficiency.
abstract: The properties of an Fe(3+)-peptide complex containing 5.6% Fe, obtained by the reaction of ferric chloride with an enzymatic hydrolysate of casein, are described. The major site of iron binding corresponds primarily to the carboxylate groups and to a lesser extent to the peptide bonds. The Fe(3+)-peptide complex is insoluble at acid pH and completely soluble at neutral to alkaline pH. When soluble, the Fe(3+) is tightly bound to the complex peptide mixture but can be displaced and complexed by a low molecular weight ligand such as cysteine. Its efficacy in relation to iron sulfate was compared in rats. Both iron sources were administrated in Milli-Q water by gastric gavage to male Wistar rats (180-200 g) after an 18 h fast with water ad libitum. Fe(3+) from the Fe(3+)-peptide complex was transferred to the blood in a dose-dependent manner (1-8 mg of Fe/kg), and the serum iron levels were significantly higher (p < 0.001) than in a similar group of rats treated with iron sulfate. In the comparative kinetics experiments, the rats received 4 mg of Fe/kg. Both iron sources presented maximum absorption, as indicated by the elevation of serum iron levels, 30 min after administration, and the AUC(0)(-->2h) of the Fe(3+)-peptide complex was significantly higher (p < 0.05) than that observed with iron sulfate. The simultaneous administration of free peptides (0-192 mg) with the Fe(3+)-peptide complex or iron sulfate did not modify the extent of absorption of iron from both sources, suggesting that the absorption is due to the complex formed and probably not to exchange reactions in the gastrointestinal tract. In the hemoglobin repletion experiments carried out on newly weaned rats with anemia induced by a low-iron diet, supplementation of the diet with the the Fe(3+)-peptide complex was as efficient as supplementation with iron sulfate in the conversion from diet to hemoglobin iron. These results, taken together, suggest that the Fe(3+)-peptide complex is a potential compound for use as an iron source in biological situations.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Chaud
authors.forename: Clarice
authors.initials: C
authors.lastname: Izumi
authors.forename: Zeki
authors.initials: Z
authors.lastname: Nahaal
authors.forename: Tadao
authors.initials: T
authors.lastname: Shuhama
authors.forename: Maria de Lourdes Pires
authors.initials: Mde L
authors.lastname: Bianchi
authors.forename: Osvaldo
authors.initials: O
authors.lastname: de Freitas
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000628:therapy; D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002712:Chlorides; D004032:Diet; D005290:Ferric Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007408:Intestinal Absorption; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013270:Stomach / Q000187:drug effects
chemical_list: D002364:Caseins; D002712:Chlorides; D005290:Ferric Compounds; D006454:Hemoglobins; D019266:Iron, Dietary; D010455:Peptides; C024823:ferric sulfate; D012965:Sodium Chloride; D007501:Iron; C024555:ferric chloride