title: Effects of ferric citrate supplementation on advanced glycation end products in a rat model of streptozotocin/nicotinamide-induced diabetes.
abstract: Diabetes is associated with the increased risks of anemia and activation of advanced glycation end products (AGEs) and the receptor for AGEs (RAGE). However, the effects of pharmacological doses of iron supplementation on AGE metabolism are less clear. The aim was to investigate the effect of ferric citrate supplementation on AGE metabolism.
  
  
  
  Diabetes was induced in overnight starved rats by intraperitoneal injections of 40 mg/kg streptozotocin and 120 mg/kg nicotinamide. Diabetic rats were fed a standard diet or pharmacological doses of ferric citrate (0.5, 1, 2, and 3 g of ferric iron/kg diet) for 10 weeks. Ferric citrate supplementation showed a dose-related effect on the hepatic steatosis score, malondialdehyde, cathepsin D, and glyoxalase I. A Western blot analysis revealed that >1 g of ferric iron suppressed hepatic AGE receptor 1 and high-mobility group-box 1 expressions but increased heme oxygenase-1 and RAGE expressions. Further analysis showed that high doses of ferric iron triggered sterol regulatory element-binding protein 1c, p38-mitogen-activated protein kinase, and nuclear factor-κB protein expressions.
  
  
  
  Overall, the present results suggest a dose-related effect of ferric citrate supplementation on AGE metabolism, and this effect was more evident at high iron doses (>1 g of ferric iron/kg diet).
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Chao
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Seu-Hwa
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Chao
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Nutrition, MacKay Memorial Hospital, Hsinchu Branch, Hsinchu, Taiwan.
authors.forename: Chi-Mei
authors.initials: CM
authors.lastname: Wang
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.|Nutrition Research Centre, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Jung-Su
authors.initials: JS
authors.lastname: Chang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000188:drug therapy; D005290:Ferric Compounds / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014280:Triglycerides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D014280:Triglycerides; D009536:Niacinamide; D008315:Malondialdehyde; D013311:Streptozocin; C025314:ferric citrate; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione
keywords: Advanced glycation end products; Diabetes; Iron; Liver steatosis