title: Potentiation of Doxorubicin cardiotoxicity by iron loading in a rodent model.
abstract: OBJECTIVE
  The role of iron toward doxorubicin (DOX) cardiotoxicity was studied using a rodent model of dietary carbonyl iron loading.
  
  
  BACKGROUND
  Doxorubicin, a commonly used anticancer drug, is known to cause serious and potentially life-threatening cardiotoxicity. Doxorubicin cardiotoxicity is thought to be mediated through free-radical injury.
  
  
  METHODS
  Male Sprague Dawley rats fed iron-rich chow (n = 8) and regular chow (n = 8) were treated with DOX or saline (4 animals in each arm). Cardiotoxicity was assessed using mortality, weight changes, Tc-99m annexin-V imaging, histopathology, and immunohistochemistry.
  
  
  RESULTS
  Animals fed iron-rich chow showed significantly higher DOX cardiotoxicity as evidenced by greater weight loss (107 +/- 14 g vs. 55 +/- 10 g weight loss, p < 0.05), higher annexin uptake (0.14 +/- 0.01% vs. 0.08 +/- 0.01% injected dose/g of myocardium, p < 0.05), more severe myocyte injury on electron microscopy, and significantly higher cleaved caspase-3 staining compared with regular chow fed rats given DOX. Feeding iron-rich chow alone did not result in any cardiotoxicity.
  
  
  CONCLUSIONS
  Dietary iron loading resulted in a substantially increased DOX cardiotoxicity in rats. Body iron stores as well as its bioavailability in tissue may be important independent predictors of susceptibility to DOX cardiotoxicity in man. Further clinical studies are warranted.
authors.affiliation: Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
authors.forename: Gurusher S
authors.initials: GS
authors.lastname: Panjrath
authors.forename: Virender
authors.initials: V
authors.lastname: Patel
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Valdiviezo
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.forename: Diwakar
authors.initials: D
authors.lastname: Jain
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects*; D019266:Iron, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D019266:Iron, Dietary; D004317:Doxorubicin