Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice

© 2016 Elsevier Inc. 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 rol...

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Main Authors: Kumfu S., Chattipakorn S., Fucharoen S., Chattipakorn N.
Format: Journal
Published: 2017
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84959284035&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/41978
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-419782017-09-28T04:24:33Z Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice Kumfu S. Chattipakorn S. Fucharoen S. Chattipakorn N. © 2016 Elsevier Inc. 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. Main methods Iron chelator deferoxamine (DFO), LTCC blocker, TTCC blocker and DMT1 blocker were used to determine the r oles of these channels regarding liver iron accumulation, apoptosis and iron regulatory protein expression in HT mice. 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. 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. 2017-09-28T04:24:33Z 2017-09-28T04:24:33Z 2016-04-01 Journal 00243205 2-s2.0-84959284035 10.1016/j.lfs.2016.02.082 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84959284035&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/41978
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2016 Elsevier Inc. 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. Main methods Iron chelator deferoxamine (DFO), LTCC blocker, TTCC blocker and DMT1 blocker were used to determine the r oles of these channels regarding liver iron accumulation, apoptosis and iron regulatory protein expression in HT mice. 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. 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.
format Journal
author Kumfu S.
Chattipakorn S.
Fucharoen S.
Chattipakorn N.
spellingShingle Kumfu S.
Chattipakorn S.
Fucharoen S.
Chattipakorn N.
Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
author_facet Kumfu S.
Chattipakorn S.
Fucharoen S.
Chattipakorn N.
author_sort Kumfu S.
title Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
title_short Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
title_full Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
title_fullStr Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
title_full_unstemmed Effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
title_sort effects of iron overload condition on liver toxicity and hepcidin/ferroportin expression in thalassemic mice
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84959284035&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/41978
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