title: Intravenous iron sucrose reverses anemia-induced cardiac remodeling, prevents myocardial fibrosis, and improves cardiac function by attenuating oxidative/nitrosative stress and inflammation.
abstract: BACKGROUND
  According to recent clinical trial data, correction of iron deficiency with intravenous (i.v.) iron has favorable outcomes on cardiac function. We evaluated whether i.v. iron treatment of anemic rats has favorable effect on the left ventricular (LV) performance and remodeling and the role of oxidative/nitrosative stress and inflammation in the process.
  
  
  METHODS
  After weaning, Sprague-Dawley rats were fed low iron diet for 16weeks, after which the treatment group received five weekly doses of i.v. iron sucrose (10mg Fe/kg body weight). Echocardiography of LV was performed and hematology parameters were assessed before treatment (baseline, day 0) and at the end of the study (day 29). On day 29, rats were sacrificed and extracellular expansion and fibrosis in LV and interventricular septum were evaluated together with oxidative/nitrosative stress, pro-inflammatory, and repair process markers.
  
  
  RESULTS
  Although iron sucrose treatment did not fully correct the anemia, it reversed anemia-induced cardiac remodeling as indicated by echocardiographic and tissue Doppler parameters. Treatment with iron sucrose also prevented anemia-induced myocardial fibrosis as indicated by extracellular expansion and fibrosis markers. Anemia-induced inflammation was prevented by iron sucrose as indicated by the levels of proinflammatory (TNF-α, NF-κB65) and repair process markers (HSP27, HSP70). In addition, iron sucrose treatment significantly reduced (p<0.01) anemia-induced oxidative and nitrosative stress.
  
  
  CONCLUSIONS
  Intravenous iron sucrose treatment reversed anemia-induced remodeling of LV, prevented myocardial fibrosis, and improved cardiac function by attenuating oxidative/nitrosative stress and inflammation in the heart.
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires. CONICET, Av. Pueyrredon 1640, 1118 Buenos Aires, Argentina. Electronic address: jorgetoblli@fibertel.com.ar.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires. CONICET, Av. Pueyrredon 1640, 1118 Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires. CONICET, Av. Pueyrredon 1640, 1118 Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rivas
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Giani
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Dominici
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage; D005290:Ferric Compounds / Q000008:administration & dosage*; D000077605:Ferric Oxide, Saccharated; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005937:Glucaric Acid / Q000008:administration & dosage*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D005290:Ferric Compounds; C002744:3-nitrotyrosine; D014443:Tyrosine; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
keywords: Cardiac function; Cardiac remodeling; Intravenous iron sucrose; Oxidative stress; Rat