Effects of 4-Hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on Liver Transcriptome in Rats: Implication in the Disruption of Circadian Rhythm and Fatty Acid Metabolism

Effects of 4-Hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on Liver Transcriptome in Rats:... Abstract Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1 (Nr1d1), aryl hydrocarbon receptor nuclear translocator-like protein 1 (Arntl), cryptochrome circadian clock 1 (Cry1), and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase (Ehhadh), in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase (LAP), indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor (PPAR)-related fatty acid metabolism. OH-PCB, transcriptome, Wistar rat, circadian rhythm, fatty acid metabolism © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicological Sciences Oxford University Press

Effects of 4-Hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on Liver Transcriptome in Rats: Implication in the Disruption of Circadian Rhythm and Fatty Acid Metabolism

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
ISSN
1096-6080
eISSN
1096-0929
D.O.I.
10.1093/toxsci/kfy123
Publisher site
See Article on Publisher Site

Abstract

Abstract Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1 (Nr1d1), aryl hydrocarbon receptor nuclear translocator-like protein 1 (Arntl), cryptochrome circadian clock 1 (Cry1), and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase (Ehhadh), in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase (LAP), indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor (PPAR)-related fatty acid metabolism. OH-PCB, transcriptome, Wistar rat, circadian rhythm, fatty acid metabolism © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Toxicological SciencesOxford University Press

Published: May 21, 2018

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