Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a polyhalogenated planar hydrocarbon belonging to a group of highly toxic and persistent environmental contaminants known as “dioxins”. TCDD is an animal teratogen and carcinogen that is well characterized for causing immunosuppression through activation...

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Autores principales:	Nicholas Dopkins, Wurood Hantoosh Neameh, Alina Hall, Yunjia Lai, Alex Rutkovsky, Alexa Orr Gandy, Kun Lu, Prakash S. Nagarkatti, Mitzi Nagarkatti
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity NFκB aryl hydrocarbon receptor metabolome immunity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/27901613ab4346858485e5b095d6a292
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spelling	oai:doaj.org-article:27901613ab4346858485e5b095d6a2922021-11-11T17:15:02ZEffects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile10.3390/ijms2221118011422-00671661-6596https://doaj.org/article/27901613ab4346858485e5b095d6a2922021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11801https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-00672,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a polyhalogenated planar hydrocarbon belonging to a group of highly toxic and persistent environmental contaminants known as “dioxins”. TCDD is an animal teratogen and carcinogen that is well characterized for causing immunosuppression through activation of aryl hydrocarbon receptor (AHR). In this study, we investigated the effect of exposure of mice to an acute dose of TCDD on the metabolic profile within the serum and cecal contents to better define the effects of TCDD on host physiology. Our findings demonstrated that within the circulating metabolome following acute TCDD exposure, there was significant dysregulation in the metabolism of bioactive lipids, amino acids, and carbohydrates when compared with the vehicle (VEH)-treated mice. These widespread changes in metabolite abundance were identified to regulate host immunity via modulating nuclear factor-kappa B (NF-κB) and extracellular signal-regulated protein kinase (ERK1/2) activity and work as biomarkers for a variety of organ injuries and dysfunctions that follow TCDD exposure. Within the cecal content of mice exposed to TCDD, we were able to detect changes in inflammatory markers that regulate NF-κB, markers of injury-related inflammation, and changes in lysine degradation, nicotinamide metabolism, and butanoate metabolism, which collectively suggested an immediate suppression of broad-scale metabolic processes in the gastrointestinal tract. Collectively, these results demonstrate that acute TCDD exposure results in immediate irregularities in the circulating and intestinal metabolome, which likely contribute to TCDD toxicity and can be used as biomarkers for the early detection of individual exposure.Nicholas DopkinsWurood Hantoosh NeamehAlina HallYunjia LaiAlex RutkovskyAlexa Orr GandyKun LuPrakash S. NagarkattiMitzi NagarkattiMDPI AGarticle2,3,7,8-tetrachlorodibenzo-p-dioxintoxicityNFκBaryl hydrocarbon receptormetabolomeimmunityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11801, p 11801 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity NFκB aryl hydrocarbon receptor metabolome immunity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity NFκB aryl hydrocarbon receptor metabolome immunity Biology (General) QH301-705.5 Chemistry QD1-999 Nicholas Dopkins Wurood Hantoosh Neameh Alina Hall Yunjia Lai Alex Rutkovsky Alexa Orr Gandy Kun Lu Prakash S. Nagarkatti Mitzi Nagarkatti Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
description	2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a polyhalogenated planar hydrocarbon belonging to a group of highly toxic and persistent environmental contaminants known as “dioxins”. TCDD is an animal teratogen and carcinogen that is well characterized for causing immunosuppression through activation of aryl hydrocarbon receptor (AHR). In this study, we investigated the effect of exposure of mice to an acute dose of TCDD on the metabolic profile within the serum and cecal contents to better define the effects of TCDD on host physiology. Our findings demonstrated that within the circulating metabolome following acute TCDD exposure, there was significant dysregulation in the metabolism of bioactive lipids, amino acids, and carbohydrates when compared with the vehicle (VEH)-treated mice. These widespread changes in metabolite abundance were identified to regulate host immunity via modulating nuclear factor-kappa B (NF-κB) and extracellular signal-regulated protein kinase (ERK1/2) activity and work as biomarkers for a variety of organ injuries and dysfunctions that follow TCDD exposure. Within the cecal content of mice exposed to TCDD, we were able to detect changes in inflammatory markers that regulate NF-κB, markers of injury-related inflammation, and changes in lysine degradation, nicotinamide metabolism, and butanoate metabolism, which collectively suggested an immediate suppression of broad-scale metabolic processes in the gastrointestinal tract. Collectively, these results demonstrate that acute TCDD exposure results in immediate irregularities in the circulating and intestinal metabolome, which likely contribute to TCDD toxicity and can be used as biomarkers for the early detection of individual exposure.
format	article
author	Nicholas Dopkins Wurood Hantoosh Neameh Alina Hall Yunjia Lai Alex Rutkovsky Alexa Orr Gandy Kun Lu Prakash S. Nagarkatti Mitzi Nagarkatti
author_facet	Nicholas Dopkins Wurood Hantoosh Neameh Alina Hall Yunjia Lai Alex Rutkovsky Alexa Orr Gandy Kun Lu Prakash S. Nagarkatti Mitzi Nagarkatti
author_sort	Nicholas Dopkins
title	Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
title_short	Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
title_full	Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
title_fullStr	Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
title_full_unstemmed	Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile
title_sort	effects of acute 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on the circulating and cecal metabolome profile
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/27901613ab4346858485e5b095d6a292
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Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile

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