title: The Induction of Oxidative/Nitrosative Stress, Inflammation, and Apoptosis by a Ferric Carboxymaltose Copy Compared to Iron Sucrose in a Non-Clinical Model.
abstract: BACKGROUND
  Ferric carboxymaltose is a next-generation polynuclear iron(III)-hydroxide carbohydrate complex for intravenous iron therapy belonging to the class of so-called non-biological complex drugs. The product characteristics and therapeutic performance of non-biological complex drugs are largely defined by the manufacturing process. A follow-on product, termed herein as ferric carboxymaltose similar, is available in India. Given that non-biological complex drugs may display differences in diverse product properties not characterisable by physico-chemical methods alone.
  
  
  OBJECTIVE
  The aim is to assess the effects of this ferric carboxymaltose similar in our non-clinical model in non-anaemic healthy rats.
  
  
  METHODS
  Non-anaemic rats were treated with intravenous ferric carboxymaltose similar or iron sucrose both at (40 mg iron/kg body weight), or with saline solution (control) for four weeks, after which the animals were sacrificed. Parameters for tissue iron distribution, oxidative stress, nitrosative stress, inflammation and apoptosis were assessed by immunohistomorphometry.
  
  
  RESULTS
  Ferric carboxymaltose similar resulted in deranged iron distribution versus iron sucrose originator as indicated by increased serum iron, transferrin saturation and tissue iron(III) deposits as well as decreased ferritin deposits in the liver, heart and kidneys versus iron sucrose originator. Ferric carboxymaltose similar also increased significantly oxidative/nitrosative stress, pro-inflammatory, and apoptosis markers in the liver, heart and kidneys versus iron sucrose originator.
  
  
  CONCLUSIONS
  In our rat model, ferric carboxymaltose similar had a less favourable safety profile than iron sucrose originator, adversely affecting iron deposition, oxidative and nitrosative stress, inflammatory responses, with impaired liver and kidney function.
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires , Av. Pueyrredon 1640, (1118) Buenos Aires, Argentina .
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 , 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 , Av. Pueyrredon 1640, (1118) Buenos Aires, Argentina .
authors.forename: Margarita
authors.initials: M
authors.lastname: Angerosa
keywords: Intravenous Iron; Iron deficiency; Toxicity
references.citation: Free Radic Biol Med. 2013 Dec;65:1174-94
references.pmid: 24036104
references.citation: Eur J Pharm Biopharm. 2011 Aug;78(3):480-91
references.pmid: 21439379
references.citation: Biochim Biophys Acta. 2000 Jun 15;1501(2-3):138-48
references.pmid: 10838187
references.citation: Nanomedicine (Lond). 2013 May;8(5):849-56
references.pmid: 23656268
references.citation: Drug Res (Stuttg). 2015 Jul;65(7):354-60
references.pmid: 25050519
references.citation: Nephrol Dial Transplant. 2010 Nov;25(11):3631-40
references.pmid: 20488820
references.citation: Curr Med Res Opin. 2012 Feb;28(2):241-3
references.pmid: 22181342
references.citation: Arzneimittelforschung. 1992 Dec;42(12 ):1439-52
references.pmid: 1288508
references.citation: Hosp Pharm. 2014 Jan;49(1):52-9
references.pmid: 24421564
references.citation: Biometals. 2015 Apr;28(2):279-92
references.pmid: 25609135
references.citation: AAPS J. 2014 Jan;16(1):15-21
references.pmid: 24065600
references.citation: Nephrol Dial Transplant. 2005 Jul;20(7):1443-9
references.pmid: 15855210
references.citation: Toxicol Pathol. 1993;21(3):321-6
references.pmid: 8248721
references.citation: Ther Adv Hematol. 2014 Apr;5(2):48-60
references.pmid: 24688754
references.citation: Curr Med Res Opin. 2013 Feb;29(2):141-7
references.pmid: 23252876
references.citation: J Clin Diagn Res. 2014 Oct;8(10):HD01-2
references.pmid: 25478369
references.citation: J Clin Invest. 1991 Oct;88(4):1207-15
references.pmid: 1918375
references.citation: Histochem Cell Biol. 2008 Apr;129(4):389-406
references.pmid: 18259769
references.citation: Arzneimittelforschung. 2011;61(7):399-410
references.pmid: 21899208
references.citation: Nephrol Dial Transplant. 2011 Oct;26(10):3262-7
references.pmid: 21355067
references.citation: Arzneimittelforschung. 2010;60(6a):345-53
references.pmid: 20648926
references.citation: Inflamm Allergy Drug Targets. 2012 Feb;11(1):66-78
references.pmid: 22309085
references.citation: Br J Haematol. 2003 Mar;120(5):853-9
references.pmid: 12614222