Modification of hepatic iron metabolism induced by pravastatin during obstructive cholestasis in rats
| Autor: | Eva Brcakova, Gabriela Kolouchova, Leos Fuksa, Petra Hirsova, Hana Lastuvkova, Jolana Cermanova, Jaroslav Mokry, Petr Nachtigal, Stanislav Micuda |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Iron medicine.medical_treatment Transferrin receptor General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Hepcidins Cholestasis Hepcidin Internal medicine medicine Animals Rats Wistar General Pharmacology Toxicology and Pharmaceutics Cation Transport Proteins Saline Heme Pravastatin biology General Medicine Metabolism medicine.disease Rats Ferritin Disease Models Animal Endocrinology Gene Expression Regulation Liver chemistry biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors Heme Oxygenase-1 Antimicrobial Cationic Peptides medicine.drug |
| Zdroj: | Life Sciences. 89:717-724 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2011.08.014 |
| Popis: | 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 (1 mg/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. |
| Databáze: | OpenAIRE |
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