title: Comparative study of gastrointestinal tract and liver toxicity of ferrous sulfate, iron amino chelate and iron polymaltose complex in normal rats.
abstract: Iron deficiency is a common worldwide problem leading to several morbidities including anemia. Although oral iron is the first choice in iron deficiency therapy, it may produce gastrointestinal (GI) and liver disorders. The aim of our study was to evaluate: (1) acute toxicity (LD(50)) in different oral iron compounds such as ferrous sulfate (FS), iron amino chelate (AC) and iron polymaltose complex (IPC) and (2) possible differences in early and late toxicity in the GI tract and liver between them.
  
  
  METHODS
  Hematological variables, liver enzymes, oxidative stress markers (thiobarbituric-acid-reactive substances, reduced glutathione, catalase, glutathione peroxidase, CuZn superoxide dysmutase) in intestinal mucosa and liver homogenates, and morphological parameters (gross anatomy, histology) were evaluated in non-anemic rats.
  
  
  RESULTS
  LD(50) was lower (p < 0.01) in FS versus iron AC and IPC. The liver enzymes were increased in the FS group (p < 0.05). The FS group presented gastric mucosal erosions and the iron AC group showed submucosal hemorrhages in the lower GI tract (colon and rectum) versus the IPC and control groups. In the small intestine, the villi/crypt ratio and goblet cells per villus were significantly (p < 0.01) reduced in the FS and iron AC groups versus IPC. The eosinophils per villus were increased (p < 0.01) in the FS and iron AC groups versus the IPC and control groups. Ferritin was elevated (p < 0.01) in the IPC group versus FS and iron AC in the small intestine and liver. The oxidative stress markers were all significantly (p < 0.01) altered in the FS and iron AC groups versus the IPC and control groups in the intestinal mucosa and liver.
  
  
  CONCLUSIONS
  FS exhibited important acute toxicity as well as early and late GI tract and liver toxicity. Despite showing similar LD(50) as IPC, iron AC presented differences regarding early and late GI tract and liver toxicity versus IPC.
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina. jorgetoblli@fibertel.com.ar
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Toblli
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.forename: Leda
authors.initials: L
authors.lastname: Olivieri
authors.forename: Margarita
authors.initials: M
authors.lastname: Angerosa
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000633:toxicity*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; C020748:ferrous sulfate; D005293:Ferritins; C013276:teferrol