Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous pollutant that results in hepatotoxicity. However, an understanding of the systematic mechanism of hepatic injury caused by DEHP remains limited. Here, we performed a comprehensive metabolomics and transcriptomics analyses to describe hepatic respons...

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Autores principales:	Gang Li, Chen-Yang Zhao, Qian Wu, Si-yuan Guan, Hong-Wei Jin, Xiao-Lin Na, Yun-Bo Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Di(2-ethylhexyl) phthalate Metabolomics Transcriptomics Hepatotoxicity Oxidative stress Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/0e05586acce84a35af33a8cc6fad52d3
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spelling	oai:doaj.org-article:0e05586acce84a35af33a8cc6fad52d32021-11-22T04:16:33ZIntegrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver0147-651310.1016/j.ecoenv.2021.112988https://doaj.org/article/0e05586acce84a35af33a8cc6fad52d32021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011003https://doaj.org/toc/0147-6513Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous pollutant that results in hepatotoxicity. However, an understanding of the systematic mechanism of hepatic injury caused by DEHP remains limited. Here, we performed a comprehensive metabolomics and transcriptomics analyses to describe hepatic responses of rats to long-term DEHP exposure and, together with pathology and functional injury of liver, systematically analyzed the pathogenesis and mechanisms of liver damage. SD rats were exposed to 0 and 600 mg/kg/day DEHP for 12 weeks. Thereafter, biochemical indicators and histopathological changes regarding liver function were detected. Metabolomics and transcriptomics profiles of rat liver samples were analyzed using a UPLC-MS/MS system and Illumina Hiseq 4000, respectively. DEHP induced hepatocyte structural alterations and edema, depressed monooxygenase activity, decreased antioxidant activities, aggravated oxidative damage, blocked the tricarboxylic acid cycle and respiratory chain, and disturbed glucose homeostasis in the liver. These findings indicate that reactive oxygen species play a major role in these events. Overall, this study systematically depicts the comprehensive mechanisms of long-term DEHP exposure to liver injury and highlights the power of metabolomics and transcriptomics platforms in the mechanistic understanding of xenobiotic hepatotoxicity.Gang LiChen-Yang ZhaoQian WuSi-yuan GuanHong-Wei JinXiao-Lin NaYun-Bo ZhangElsevierarticleDi(2-ethylhexyl) phthalateMetabolomicsTranscriptomicsHepatotoxicityOxidative stressEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 112988- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Di(2-ethylhexyl) phthalate Metabolomics Transcriptomics Hepatotoxicity Oxidative stress Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Di(2-ethylhexyl) phthalate Metabolomics Transcriptomics Hepatotoxicity Oxidative stress Environmental pollution TD172-193.5 Environmental sciences GE1-350 Gang Li Chen-Yang Zhao Qian Wu Si-yuan Guan Hong-Wei Jin Xiao-Lin Na Yun-Bo Zhang Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
description	Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous pollutant that results in hepatotoxicity. However, an understanding of the systematic mechanism of hepatic injury caused by DEHP remains limited. Here, we performed a comprehensive metabolomics and transcriptomics analyses to describe hepatic responses of rats to long-term DEHP exposure and, together with pathology and functional injury of liver, systematically analyzed the pathogenesis and mechanisms of liver damage. SD rats were exposed to 0 and 600 mg/kg/day DEHP for 12 weeks. Thereafter, biochemical indicators and histopathological changes regarding liver function were detected. Metabolomics and transcriptomics profiles of rat liver samples were analyzed using a UPLC-MS/MS system and Illumina Hiseq 4000, respectively. DEHP induced hepatocyte structural alterations and edema, depressed monooxygenase activity, decreased antioxidant activities, aggravated oxidative damage, blocked the tricarboxylic acid cycle and respiratory chain, and disturbed glucose homeostasis in the liver. These findings indicate that reactive oxygen species play a major role in these events. Overall, this study systematically depicts the comprehensive mechanisms of long-term DEHP exposure to liver injury and highlights the power of metabolomics and transcriptomics platforms in the mechanistic understanding of xenobiotic hepatotoxicity.
format	article
author	Gang Li Chen-Yang Zhao Qian Wu Si-yuan Guan Hong-Wei Jin Xiao-Lin Na Yun-Bo Zhang
author_facet	Gang Li Chen-Yang Zhao Qian Wu Si-yuan Guan Hong-Wei Jin Xiao-Lin Na Yun-Bo Zhang
author_sort	Gang Li
title	Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
title_short	Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
title_full	Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
title_fullStr	Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
title_full_unstemmed	Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
title_sort	integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/0e05586acce84a35af33a8cc6fad52d3
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Integrated metabolomics and transcriptomics reveal di(2-ethylhexyl) phthalate-induced mitochondrial dysfunction and glucose metabolism disorder through oxidative stress in rat liver

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