title: Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice.
abstract: OBJECTIVE
  Although iron-overload conditions can be found in β-thalassemic patients, resulting in cellular damage, particularly in the liver, the mechanism for this iron-mediated hepatic injury specifically in β-thalassemic (HT) mice is unclear. This study aimed to investigate the roles of L-type calcium channels (LTCC), T-type calcium channels (TTCC) and divalent metal transporter1 (DMT1) in iron-mediated hepatic injury in HT mice.
  
  
  METHODS
  Iron chelator deferoxamine (DFO), LTCC blocker, TTCC blocker and DMT1 blocker were used to determine the roles of these channels regarding liver iron accumulation, apoptosis and iron regulatory protein expression in HT mice.
  
  
  RESULTS
  TTCC and DMT1 blockers and DFO decreased liver iron and malondialdehyde (MDA) in HT mice indicating their antioxidant effects, whereas LTCC blocker produced no decrease in liver iron or MDA. However, only DFO decreased liver apoptosis through the reduced Bax/Bcl-2 ratio in wild type (WT) mice. The levels of iron regulatory hormone hepcidin were markedly higher in HT mice even before iron loading while ferroportin levels did not alter. Each of the pharmacological interventions increased ferroportin protein back to normal levels only in WT while HT mice showed no difference.
  
  
  CONCLUSIONS
  Thalassemic mice have different hepcidin/ferroportin and apoptotic protein expression as a defense mechanism to iron-overload compared with those in WT mice. DFO was the most effective intervention in preventing liver apoptosis under iron-overload conditions in WT but did not have the same effect in HT mice.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sirinart
authors.initials: S
authors.lastname: Kumfu
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.affiliation: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand. Electronic address: nchattip@gmail.com.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003676:Deferoxamine / Q000627:therapeutic use; D015870:Gene Expression; D064451:Hepcidins / Q000096:biosynthesis* / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D013789:Thalassemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D027682:Cation Transport Proteins; D003676:Deferoxamine; D064451:Hepcidins; D007501:Iron; D007502:Iron Chelating Agents; D051028:bcl-2-Associated X Protein; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C494827:Bax protein, mouse; C500556:SLC39A14 protein, mouse
keywords: Hepcidin; Iron-overload; Liver apoptosis; Oxidative stress; Thalassemia