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Hepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic study

2019Journal article Open access
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dc.contributor.authorAraújo, Ana Margarida
dc.contributor.authorEnea, Maria
dc.contributor.authorCarvalho, Félix
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorCarvalho, Márcia
dc.contributor.authorGuedes de Pinho, Paula
dc.date.accessioned2021-06-29T16:46:29Z
dc.date.available2021-06-29T16:46:29Z
dc.date.issued2019
dc.description.abstractLiver 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/metabo9100228pt_PT
dc.identifier.issn2218-1989
dc.identifier.urihttp://hdl.handle.net/10284/9973
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationThis research was funded by European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2019.pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHeat stresspt_PT
dc.subjectPrimary mouse hepatocytespt_PT
dc.subjectMetabolic profilept_PT
dc.subjectGC-MSpt_PT
dc.subjectMultivariate statistical analysispt_PT
dc.titleHepatic metabolic derangements triggered by hyperthermia: an in vitro metabolomic studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue10pt_PT
oaire.citation.startPage228pt_PT
oaire.citation.titleMetabolitespt_PT
oaire.citation.volume9pt_PT
person.familyNameCarvalho
person.givenNameMarcia
person.identifier2017111
person.identifier.ciencia-id8B10-171E-E63E
person.identifier.orcid0000-0001-9884-4751
person.identifier.ridD-5999-2013
person.identifier.scopus-author-id7201413997
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3837b828-ba57-47f7-a811-cce65e4922c6
relation.isAuthorOfPublication.latestForDiscovery3837b828-ba57-47f7-a811-cce65e4922c6

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