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Open AccessArticle

Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study

1
UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2
UFP Energy, Environment and Health Research Unit (FP-ENAS), University Fernando Pessoa, Praça Nove de Abril, 349, 4249-004 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(10), 228; https://doi.org/10.3390/metabo9100228
Received: 20 August 2019 / Revised: 30 September 2019 / Accepted: 11 October 2019 / Published: 15 October 2019
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Background and aims: 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. View Full-Text
Keywords: heat stress; primary mouse hepatocytes; metabolic profile; GC-MS; multivariate statistical analysis heat stress; primary mouse hepatocytes; metabolic profile; GC-MS; multivariate statistical analysis
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MDPI and ACS Style

Araújo, A.M.; Enea, M.; Carvalho, F.; Bastos, M.L.; Carvalho, M.; Guedes de Pinho, P. Hepatic Metabolic Derangements Triggered by Hyperthermia: An In Vitro Metabolomic Study. Metabolites 2019, 9, 228.

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