Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress

In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) w...

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Main Authors: Julia Hernandez-Baixauli, Gertruda Chomiciute, Harry Tracey, Ignasi Mora, Antonio J. Cortés-Espinar, Javier Ávila-Román, Nerea Abasolo, Hector Palacios-Jordan, Elisabet Foguet-Romero, David Suñol, Mar Galofré, Juan María Alcaide-Hidalgo, Laura Baselga-Escudero, Josep M. del Bas, Miquel Mulero
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/13/1/67
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author Julia Hernandez-Baixauli
Gertruda Chomiciute
Harry Tracey
Ignasi Mora
Antonio J. Cortés-Espinar
Javier Ávila-Román
Nerea Abasolo
Hector Palacios-Jordan
Elisabet Foguet-Romero
David Suñol
Mar Galofré
Juan María Alcaide-Hidalgo
Laura Baselga-Escudero
Josep M. del Bas
Miquel Mulero
author_facet Julia Hernandez-Baixauli
Gertruda Chomiciute
Harry Tracey
Ignasi Mora
Antonio J. Cortés-Espinar
Javier Ávila-Román
Nerea Abasolo
Hector Palacios-Jordan
Elisabet Foguet-Romero
David Suñol
Mar Galofré
Juan María Alcaide-Hidalgo
Laura Baselga-Escudero
Josep M. del Bas
Miquel Mulero
author_sort Julia Hernandez-Baixauli
collection DOAJ
description In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; <sup>1</sup>H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., <i>Escherichia coli</i> and <i>Akkermansia muciniphila</i>) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.
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spelling doaj.art-b7dc4d1b0f7e4574ab0833690b4d744b2024-01-26T14:41:02ZengMDPI AGAntioxidants2076-39212024-01-011316710.3390/antiox13010067Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative StressJulia Hernandez-Baixauli0Gertruda Chomiciute1Harry Tracey2Ignasi Mora3Antonio J. Cortés-Espinar4Javier Ávila-Román5Nerea Abasolo6Hector Palacios-Jordan7Elisabet Foguet-Romero8David Suñol9Mar Galofré10Juan María Alcaide-Hidalgo11Laura Baselga-Escudero12Josep M. del Bas13Miquel Mulero14Eurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, SpainBrudy Technology S.L., 08006 Barcelona, SpainNutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, SpainMolecular and Applied Pharmacology Group (FARMOLAP), Department of Pharmacology, Universidad de Sevilla, 41012 Sevilla, SpainEurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Digital Health, 08005 Barcelona, SpainEurecat, Centre Tecnològic de Catalunya, Digital Health, 08005 Barcelona, SpainEurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, 43204 Reus, SpainEurecat, Centre Tecnològic de Catalunya, Àrea Biotecnologia, 43204 Reus, SpainNutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, SpainIn this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; <sup>1</sup>H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., <i>Escherichia coli</i> and <i>Akkermansia muciniphila</i>) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.https://www.mdpi.com/2076-3921/13/1/67paraquatoxidative stressmetabolismgut microbiome3-hydroxibutiric acidsphingomyelins
spellingShingle Julia Hernandez-Baixauli
Gertruda Chomiciute
Harry Tracey
Ignasi Mora
Antonio J. Cortés-Espinar
Javier Ávila-Román
Nerea Abasolo
Hector Palacios-Jordan
Elisabet Foguet-Romero
David Suñol
Mar Galofré
Juan María Alcaide-Hidalgo
Laura Baselga-Escudero
Josep M. del Bas
Miquel Mulero
Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
Antioxidants
paraquat
oxidative stress
metabolism
gut microbiome
3-hydroxibutiric acid
sphingomyelins
title Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
title_full Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
title_fullStr Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
title_full_unstemmed Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
title_short Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress
title_sort exploring metabolic and gut microbiome responses to paraquat administration in male wistar rats implications for oxidative stress
topic paraquat
oxidative stress
metabolism
gut microbiome
3-hydroxibutiric acid
sphingomyelins
url https://www.mdpi.com/2076-3921/13/1/67
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