Abstract
Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-α were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-α. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.
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Abbreviations
- BDE209:
-
2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether
- PBDEs:
-
Polybrominated diphenyl ethers
- OH-BDEs:
-
Hydroxylated polybrominated diphenyl ether
- POPs:
-
Persistent organic pollutants
- CHOL:
-
Total cholesterol
- TG:
-
Triglyceride
- ROS:
-
Reactive oxygen species
- MDA:
-
Malondialdehyde
- GSH:
-
Reduced glutathione
- SOD:
-
Superoxide dismutase
- TNF-α:
-
Tumor necrosis factor α
- MHC:
-
Major histocompatibility complex
- T1DM:
-
Type I diabetes mellitus
- NOD:
-
Nonobese diabetic
- GO:
-
Gene ontology
- ELISA:
-
Enzyme-linked immunosorbent assays
- qRT-PCR:
-
Real-time quantitative reverse transcription polymerase chain reaction
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Acknowledgments
The authors wish to thank Drs. Dai Chen and Jie Zong (Novel Bioinformatics Ltd., Co, Shanghai, China) for their technical assistance in bioinformatics analysis. This work was supported by Environmental Protection Research Special Funds for Public Welfare Projects (200909054), National 973 program (2009CB941701), National Natural Science Foundation of China (81172695, 30972508), Doctoral Fund of Ministry of Education of China (20093234110002), Six talents peak project of Jiangsu province (DG216D5047), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), China.
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No competing financial interests exist.
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Zhan Zhang and Zhen-Zhen Sun contributed equally to this work.
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Zhang, Z., Sun, ZZ., Xiao, X. et al. Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver. Arch Toxicol 87, 1557–1567 (2013). https://doi.org/10.1007/s00204-013-1059-8
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DOI: https://doi.org/10.1007/s00204-013-1059-8