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Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice.
- Source :
-
Life sciences [Life Sci] 2016 Apr 01; Vol. 150, pp. 15-23. Date of Electronic Publication: 2016 Feb 24. - Publication Year :
- 2016
-
Abstract
- Aims: 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.<br />Main 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.<br />Key Findings: 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.<br />Significance: 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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Calcium Channel Blockers therapeutic use
Calcium Channels, L-Type drug effects
Calcium Channels, L-Type metabolism
Calcium Channels, T-Type drug effects
Calcium Channels, T-Type metabolism
Cation Transport Proteins genetics
Deferoxamine therapeutic use
Gene Expression
Hepcidins genetics
Iron metabolism
Iron Chelating Agents therapeutic use
Iron Overload complications
Mice, Inbred C57BL
Thalassemia genetics
bcl-2-Associated X Protein biosynthesis
bcl-2-Associated X Protein genetics
Ferroportin
Cation Transport Proteins biosynthesis
Chemical and Drug Induced Liver Injury pathology
Hepcidins biosynthesis
Iron Overload metabolism
Thalassemia metabolism
Thalassemia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 150
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 26921633
- Full Text :
- https://doi.org/10.1016/j.lfs.2016.02.082