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Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine
Intracellular calcium [Ca(2+)](i) dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347387/ https://www.ncbi.nlm.nih.gov/pubmed/28287621 http://dx.doi.org/10.1038/srep44460 |
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author | Wongjaikam, Suwakon Kumfu, Sirinart Khamseekaew, Juthamas Chattipakorn, Siriporn C. Chattipakorn, Nipon |
author_facet | Wongjaikam, Suwakon Kumfu, Sirinart Khamseekaew, Juthamas Chattipakorn, Siriporn C. Chattipakorn, Nipon |
author_sort | Wongjaikam, Suwakon |
collection | PubMed |
description | Intracellular calcium [Ca(2+)](i) dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)](i) homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca(2+)]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca(2+)]i homeostasis, only DFP + NAC restored cardiac [Ca(2+)]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca(2+)](i) homeostasis, leading to restored myocardial contractility in iron-overloaded rats. |
format | Online Article Text |
id | pubmed-5347387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53473872017-03-14 Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine Wongjaikam, Suwakon Kumfu, Sirinart Khamseekaew, Juthamas Chattipakorn, Siriporn C. Chattipakorn, Nipon Sci Rep Article Intracellular calcium [Ca(2+)](i) dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca(2+)](i) homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca(2+)]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca(2+)]i homeostasis, only DFP + NAC restored cardiac [Ca(2+)]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca(2+)](i) homeostasis, leading to restored myocardial contractility in iron-overloaded rats. Nature Publishing Group 2017-03-13 /pmc/articles/PMC5347387/ /pubmed/28287621 http://dx.doi.org/10.1038/srep44460 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wongjaikam, Suwakon Kumfu, Sirinart Khamseekaew, Juthamas Chattipakorn, Siriporn C. Chattipakorn, Nipon Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title | Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title_full | Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title_fullStr | Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title_full_unstemmed | Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title_short | Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine |
title_sort | restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and n-acetyl cysteine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347387/ https://www.ncbi.nlm.nih.gov/pubmed/28287621 http://dx.doi.org/10.1038/srep44460 |
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