Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/57963 http://dx.doi.org/10.1371/journal.pone.0149630 |
Resumo: | Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations. |
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Vasques, Enio RodriguesMonteiro Cunha, Jose EduardoMendonca Coelho, Ana MariaSampietre, Sandra N.Patzina, Rosely AntunesAbdo, Emilio EliasNader, Helena B. [UNIFESP]Tersariol, Ivarne L. S. [UNIFESP]Lima, Marcelo Andrade [UNIFESP]Godoy, Carlos M. G. [UNIFESP]Rodrigues, TiagoChaib, EleazarD'Albuquerque, Luiz A. C.2020-08-21T17:00:22Z2020-08-21T17:00:22Z2016Plos One. San Francisco, v. 11, n. 2, p. -, 2016.1932-6203https://repositorio.unifesp.br/handle/11600/57963http://dx.doi.org/10.1371/journal.pone.0149630WOS000371276100115.pdf10.1371/journal.pone.0149630WOS:000371276100115Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 37, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Dept Biochem, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Dept Sci & Technol, Sao Paulo, BrazilFed Univ ABC, Ctr Nat & Human Sci, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Dept Biochem, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP, Dept Sci & Technol, Sao Paulo, BrazilWeb of Science-engPublic Library SciencePlos OneTrisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSan Francisco112info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/579632021-09-29 09:32:03.179metadata only accessoai:repositorio.unifesp.br:11600/57963Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652021-09-29T12:32:03Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
title |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
spellingShingle |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion Vasques, Enio Rodrigues |
title_short |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
title_full |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
title_fullStr |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
title_full_unstemmed |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
title_sort |
Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion |
author |
Vasques, Enio Rodrigues |
author_facet |
Vasques, Enio Rodrigues Monteiro Cunha, Jose Eduardo Mendonca Coelho, Ana Maria Sampietre, Sandra N. Patzina, Rosely Antunes Abdo, Emilio Elias Nader, Helena B. [UNIFESP] Tersariol, Ivarne L. S. [UNIFESP] Lima, Marcelo Andrade [UNIFESP] Godoy, Carlos M. G. [UNIFESP] Rodrigues, Tiago Chaib, Eleazar D'Albuquerque, Luiz A. C. |
author_role |
author |
author2 |
Monteiro Cunha, Jose Eduardo Mendonca Coelho, Ana Maria Sampietre, Sandra N. Patzina, Rosely Antunes Abdo, Emilio Elias Nader, Helena B. [UNIFESP] Tersariol, Ivarne L. S. [UNIFESP] Lima, Marcelo Andrade [UNIFESP] Godoy, Carlos M. G. [UNIFESP] Rodrigues, Tiago Chaib, Eleazar D'Albuquerque, Luiz A. C. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Vasques, Enio Rodrigues Monteiro Cunha, Jose Eduardo Mendonca Coelho, Ana Maria Sampietre, Sandra N. Patzina, Rosely Antunes Abdo, Emilio Elias Nader, Helena B. [UNIFESP] Tersariol, Ivarne L. S. [UNIFESP] Lima, Marcelo Andrade [UNIFESP] Godoy, Carlos M. G. [UNIFESP] Rodrigues, Tiago Chaib, Eleazar D'Albuquerque, Luiz A. C. |
description |
Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2020-08-21T17:00:22Z |
dc.date.available.fl_str_mv |
2020-08-21T17:00:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco, v. 11, n. 2, p. -, 2016. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/57963 http://dx.doi.org/10.1371/journal.pone.0149630 |
dc.identifier.issn.none.fl_str_mv |
1932-6203 |
dc.identifier.file.none.fl_str_mv |
WOS000371276100115.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0149630 |
dc.identifier.wos.none.fl_str_mv |
WOS:000371276100115 |
identifier_str_mv |
Plos One. San Francisco, v. 11, n. 2, p. -, 2016. 1932-6203 WOS000371276100115.pdf 10.1371/journal.pone.0149630 WOS:000371276100115 |
url |
https://repositorio.unifesp.br/handle/11600/57963 http://dx.doi.org/10.1371/journal.pone.0149630 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Plos One |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
- |
dc.coverage.none.fl_str_mv |
San Francisco |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
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