title: Modification of hepatic iron metabolism induced by pravastatin during obstructive cholestasis in rats.
abstract: OBJECTIVE
  To evaluate iron biochemistry and contributing liver mechanisms during obstructive cholestasis and pravastatin treatment in rats.
  
  
  METHODS
  A rat model of cholestasis induced by bile duct ligation (BDL) was used for the study. The detection of iron and the expression of relevant molecules were performed one week after surgery in the control, and cholestatic animals after treatment with either saline or pravastatin (1mg/kg/day).
  
  
  RESULTS
  Saline-administered BDL rats showed, in comparison to sham-operated animals, a significant increase in plasma iron concentration, increased liver protein content of heme oxygenase-1 (HO-1) and a decline in the expression of hepcidin. Ferroportin 1 expression was increased with a simultaneous reduction in intrahepatic iron concentration. The administration of pravastatin to BDL animals attenuated proliferation changes in liver parenchyma, prevented HO-1 induction, restored hepatic mRNA hepcidin expression to control levels and induced the expression of ferritin, transferrin receptors (TfR1/2) and divalent metal transporter-1. This was accompanied by an increased content of intrahepatic iron when compared to the BDL animals, and a reduction of hyperbilirubinemia.
  
  
  CONCLUSIONS
  Cholestasis-induced increase in plasma and decrease in hepatic iron levels were associated with up-regulation of liver HO-1 and ferroportin 1. Pravastatin alleviated cholestatic liver impairment and raised liver iron content by modulation of heme catabolism and an increase of hepatic iron uptake and storage capacity.
authors.affiliation: Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Czech Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kolouchova
authors.forename: Eva
authors.initials: E
authors.lastname: Brcakova
authors.forename: Petra
authors.initials: P
authors.lastname: Hirsova
authors.forename: Jolana
authors.initials: J
authors.lastname: Cermanova
authors.forename: Leos
authors.initials: L
authors.lastname: Fuksa
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mokry
authors.forename: Petr
authors.initials: P
authors.lastname: Nachtigal
authors.forename: Hana
authors.initials: H
authors.lastname: Lastuvkova
authors.forename: Stanislav
authors.initials: S
authors.lastname: Micuda
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D002779:Cholestasis / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D064451:Hepcidins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578703:Hamp protein, rat; D064451:Hepcidins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000098742:Ferroportin; D007501:Iron; D051547:Heme Oxygenase-1; D017035:Pravastatin