Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue

Abstract We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine...

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Autores principales:	Israel Ramirez-Sanchez, Viridiana Navarrete-Yañez, Alejandra Garate-Carrillo, Modesto Lara-Hernandez, Judith Espinosa-Raya, Aldo Moreno-Ulloa, Benjamin Gomez-Diaz, Ana Lilia Cedeño-Garcidueñas, Guillermo Ceballos, Francisco Villarreal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2587dffb9d514fddbd6175c172874b01
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spelling	oai:doaj.org-article:2587dffb9d514fddbd6175c172874b012021-11-14T12:20:38ZRestorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue10.1038/s41598-021-01093-w2045-2322https://doaj.org/article/2587dffb9d514fddbd6175c172874b012021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01093-whttps://doaj.org/toc/2045-2322Abstract We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.Israel Ramirez-SanchezViridiana Navarrete-YañezAlejandra Garate-CarrilloModesto Lara-HernandezJudith Espinosa-RayaAldo Moreno-UlloaBenjamin Gomez-DiazAna Lilia Cedeño-GarcidueñasGuillermo CeballosFrancisco VillarrealNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Israel Ramirez-Sanchez Viridiana Navarrete-Yañez Alejandra Garate-Carrillo Modesto Lara-Hernandez Judith Espinosa-Raya Aldo Moreno-Ulloa Benjamin Gomez-Diaz Ana Lilia Cedeño-Garcidueñas Guillermo Ceballos Francisco Villarreal Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
description	Abstract We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.
format	article
author	Israel Ramirez-Sanchez Viridiana Navarrete-Yañez Alejandra Garate-Carrillo Modesto Lara-Hernandez Judith Espinosa-Raya Aldo Moreno-Ulloa Benjamin Gomez-Diaz Ana Lilia Cedeño-Garcidueñas Guillermo Ceballos Francisco Villarreal
author_facet	Israel Ramirez-Sanchez Viridiana Navarrete-Yañez Alejandra Garate-Carrillo Modesto Lara-Hernandez Judith Espinosa-Raya Aldo Moreno-Ulloa Benjamin Gomez-Diaz Ana Lilia Cedeño-Garcidueñas Guillermo Ceballos Francisco Villarreal
author_sort	Israel Ramirez-Sanchez
title	Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
title_short	Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
title_full	Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
title_fullStr	Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
title_full_unstemmed	Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue
title_sort	restorative potential of (−)-epicatechin in a rat model of gulf war illness muscle atrophy and fatigue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2587dffb9d514fddbd6175c172874b01
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Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue

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