title: New rat models of iron sucrose-induced iron overload.
abstract: The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.
authors.affiliation: Peritox Laboratory (Périnatalité et Risques Toxiques) Faculty of Medicine, Picardy Jules Verne University, 3 rue des Louvels, Amiens, France.
authors.forename: Bá
authors.initials: B
authors.lastname: Vu'o'ng Lê
authors.forename: Hafida
authors.initials: H
authors.lastname: Khorsi-Cauet
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Villegier
authors.forename: Véronique
authors.initials: V
authors.lastname: Bach
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gay-Quéheillard
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D000077605:Ferric Oxide, Saccharated; D015870:Gene Expression; D005937:Glucaric Acid; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000175:diagnosis / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D044967:Serum / Q000737:chemistry; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D005290:Ferric Compounds; C578702:HAMP protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid