Modification of hepatic iron metabolism induced by pravastatin during obstructive cholestasis in rats
2011
Kolouchova, Gabriela | Brcakova, Eva | Hirsova, Petra | Cermanova, Jolana | Fuksa, Leos | Mokry, Jaroslav | Nachtigal, Petr | Lastuvkova, Hana | Micuda, Stanislav
AIMS: To evaluate iron biochemistry and contributing liver mechanisms during obstructive cholestasis and pravastatin treatment in rats. MAIN 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). KEY FINDINGS: 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. SIGNIFICANCE: 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.
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