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Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats
Gong, Yufeng1; Zhang, Haijun1; Geng, Ningbo1; Xing, Liguo2; Fan, Jingfeng3; Luo, Yun1,4; Song, Xiaoyao1; Ren, Xiaoqian1,4; Wang, Feidi1,4; Chen, Jiping1
KeywordShort-chain Chlorinated Paraffins Thyroid Disruption Hepatic Metabolism Thyroid Hormone Constitutive Androstane Receptor
Source PublicationSCIENCE OF THE TOTAL ENVIRONMENT
2018-06-01
ISSN0048-9697
DOI10.1016/j.scitotenv.2017.12.251
Volume625Pages:657-666
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectEnvironmental Sciences
WOS Research AreaEnvironmental Sciences & Ecology
WOS KeywordARYL-HYDROCARBON RECEPTOR ; POLYBROMINATED DIPHENYL ETHERS ; HUMAN EXPOSURE ; POLYCHLORINATED-BIPHENYLS ; ENVIRONMENTAL CHEMICALS ; LACTATIONAL EXPOSURE ; IN-VIVO ; CHINA ; CAR ; METABOLISM
AbstractShort-chain chlorinated paraffins (SCCPs) are known to disturb thyroid hormone (TH) homeostasis in rodents. However, the mechanism remains to be fully characterized. In this study, male Sprague Dawley rats received SCCPs (0, 1, 10, or 100 mg/kg/day) via gavage once a day for consecutive 28 days. Plasma and hepatic TH concentrations, thyrocyte structure, as well as thyroid and hepatic mRNA and protein levels of genes associated with TH homeostasis were examined. Moreover, we performed molecular docking to predict interactions between constitutive androstane receptor (CAR), a key regulator in xenobiotic-induced TH metabolism, with different SCCP molecules. Exposure to SCCPs significantly decreased the circulating free thyroxine (T-4) and triiodothyronine (T-3) levels, but increased thyroid-stimulating hormone (TSH) levels by a feedback mechanism. Decreased hepatic T-4 and increased hepatic T-3 levels were also seen after 100 mg/kg/day SCCPs exposure. SCCPs didn't show any significant effects on the expression of thyroid TH synthesis genes or thyrocyte structure. However, stimulation effects were observed for mRNA and protein levels of hepatic uridine diphosphoglucuronosyl transferase (UGT) 1A1 and organic anion transporter 2, suggesting an accelerated TH metabolism in rat liver. The increased cytochrome P450 2B1 but not 1A1 mRNA and protein levels indicated that the CAR signaling was activated by SCCPs exposure. According to docking analysis, SCCPs form hydrophobic interactions with CAR and the binding affinity shows dependency on chlorine content. Overall, our data showed that CAR implicated enhancement of hepatic TH influx and degradation could be the main cause for SCCPs induced TH deficiency in male rats. (C) 2017 Elsevier B.V. All rights reserved.
Language英语
WOS IDWOS:000426356600067
PublisherELSEVIER SCIENCE BV
Citation statistics
Cited Times:5[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/168813
Collection中国科学院大连化学物理研究所
Corresponding AuthorChen, Jiping
Affiliation1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
2.Shenyang Res Inst Chem Ind Ltd, Safety Evaluat Ctr, Shenyang 110021, Liaoning, Peoples R China
3.Natl Marine Environm Monitoring Ctr, Dalian 116023, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Gong, Yufeng,Zhang, Haijun,Geng, Ningbo,et al. Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2018,625:657-666.
APA Gong, Yufeng.,Zhang, Haijun.,Geng, Ningbo.,Xing, Liguo.,Fan, Jingfeng.,...&Chen, Jiping.(2018).Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.SCIENCE OF THE TOTAL ENVIRONMENT,625,657-666.
MLA Gong, Yufeng,et al."Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats".SCIENCE OF THE TOTAL ENVIRONMENT 625(2018):657-666.
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