Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10284/9973 |
Resumo: | Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage. |
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7160 |
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Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic studyHeat stressPrimary mouse hepatocytesMetabolic profileGC-MSMultivariate statistical analysisLiver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage.MDPIRepositório Institucional da Universidade Fernando PessoaAraújo, Ana MargaridaEnea, MariaCarvalho, FélixBastos, Maria de LourdesCarvalho, MárciaGuedes de Pinho, Paula2021-06-29T16:46:29Z2019-01-01T00:00:00Z2019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/9973eng2218-198910.3390/metabo9100228info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-09-06T02:09:16Zoai:bdigital.ufp.pt:10284/9973Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:46:45.193906Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
title |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
spellingShingle |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study Araújo, Ana Margarida Heat stress Primary mouse hepatocytes Metabolic profile GC-MS Multivariate statistical analysis |
title_short |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
title_full |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
title_fullStr |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
title_full_unstemmed |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
title_sort |
Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study |
author |
Araújo, Ana Margarida |
author_facet |
Araújo, Ana Margarida Enea, Maria Carvalho, Félix Bastos, Maria de Lourdes Carvalho, Márcia Guedes de Pinho, Paula |
author_role |
author |
author2 |
Enea, Maria Carvalho, Félix Bastos, Maria de Lourdes Carvalho, Márcia Guedes de Pinho, Paula |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Araújo, Ana Margarida Enea, Maria Carvalho, Félix Bastos, Maria de Lourdes Carvalho, Márcia Guedes de Pinho, Paula |
dc.subject.por.fl_str_mv |
Heat stress Primary mouse hepatocytes Metabolic profile GC-MS Multivariate statistical analysis |
topic |
Heat stress Primary mouse hepatocytes Metabolic profile GC-MS Multivariate statistical analysis |
description |
Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-01-01T00:00:00Z 2019-01-01T00:00:00Z 2021-06-29T16:46:29Z |
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.uri.fl_str_mv |
http://hdl.handle.net/10284/9973 |
url |
http://hdl.handle.net/10284/9973 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2218-1989 10.3390/metabo9100228 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799130333795319808 |