Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone

The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygou...

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Main Authors: Paranee Yatmark, Noppawan Phumala Morales, Urai Chaisri, Surasak Wichaiyo, Warinkarn Hemstapat, Somdet Srichairatanakool, Saovaros Svasti, Suthat Fucharoen
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Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/45448
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spelling th-cmuir.6653943832-454482018-01-24T06:10:34Z Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone Paranee Yatmark Noppawan Phumala Morales Urai Chaisri Surasak Wichaiyo Warinkarn Hemstapat Somdet Srichairatanakool Saovaros Svasti Suthat Fucharoen The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice ( mu β th-3/+ , BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators. © 2014 Elsevier GmbH. 2018-01-24T06:10:34Z 2018-01-24T06:10:34Z 2014-01-01 Journal 16181433 09402993 2-s2.0-84902819565 10.1016/j.etp.2014.03.002 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84902819565&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/45448
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice ( mu β th-3/+ , BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators. © 2014 Elsevier GmbH.
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author Paranee Yatmark
Noppawan Phumala Morales
Urai Chaisri
Surasak Wichaiyo
Warinkarn Hemstapat
Somdet Srichairatanakool
Saovaros Svasti
Suthat Fucharoen
spellingShingle Paranee Yatmark
Noppawan Phumala Morales
Urai Chaisri
Surasak Wichaiyo
Warinkarn Hemstapat
Somdet Srichairatanakool
Saovaros Svasti
Suthat Fucharoen
Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
author_facet Paranee Yatmark
Noppawan Phumala Morales
Urai Chaisri
Surasak Wichaiyo
Warinkarn Hemstapat
Somdet Srichairatanakool
Saovaros Svasti
Suthat Fucharoen
author_sort Paranee Yatmark
title Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
title_short Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
title_full Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
title_fullStr Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
title_full_unstemmed Iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: Effects of deferoxamine and deferiprone
title_sort iron distribution and histopathological characterization of the liver and heart of β-thalassemic mice with parenteral iron overload: effects of deferoxamine and deferiprone
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84902819565&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/45448
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