Modification of hepatic iron metabolism induced by pravastatin during obstructive cholestasis in rats
Abstract
The aim of the study was to evaluate iron biochemistry and contributing liver mechanisms during obstructive cholestasis and pravastatin treatment in rats. A rat model of cholestasis induced by bile duct ligation (BDL) was used for the study.
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 mRNA 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.
In conclusion, 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.