Archives of Toxicology

, Volume 87, Issue 8, pp 1557–1567

Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver

  • Zhan Zhang
  • Zhen-Zhen Sun
  • Xue Xiao
  • Shixin Zhou
  • Xi-Chen Wang
  • Jun Gu
  • Liang-Lin Qiu
  • Xu-Hui Zhang
  • Qiujin Xu
  • Binghui Zhen
  • Xinru Wang
  • Shou-Lin Wang
Toxicogenomics

DOI: 10.1007/s00204-013-1059-8

Cite this article as:
Zhang, Z., Sun, ZZ., Xiao, X. et al. Arch Toxicol (2013) 87: 1557. doi:10.1007/s00204-013-1059-8

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.

Keywords

BDE209 Glucose homeostasis Oxidative stress Gene microarray Pathway analysis 

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

Supplementary material

204_2013_1059_MOESM1_ESM.doc (38 kb)
Supplementary material 1 (DOC 38 kb)
204_2013_1059_MOESM2_ESM.xls (282 kb)
Supplementary material 2 (XLS 282 kb)
204_2013_1059_MOESM3_ESM.xls (49 kb)
Supplementary material 3 (XLS 49 kb)
204_2013_1059_MOESM4_ESM.tif (1.5 mb)
Supplementary material 4 (TIFF 1540 kb)
204_2013_1059_MOESM5_ESM.tif (1.7 mb)
Supplementary material 5 (TIFF 1752 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Zhan Zhang
    • 1
  • Zhen-Zhen Sun
    • 1
  • Xue Xiao
    • 1
  • Shixin Zhou
    • 2
  • Xi-Chen Wang
    • 1
  • Jun Gu
    • 1
  • Liang-Lin Qiu
    • 1
  • Xu-Hui Zhang
    • 1
  • Qiujin Xu
    • 3
  • Binghui Zhen
    • 3
  • Xinru Wang
    • 1
  • Shou-Lin Wang
    • 1
  1. 1.Key Lab of Modern Toxicology of Ministry of Education, School of Public HealthNanjing Medical UniversityNanjingChina
  2. 2.Stem Cell Research Center and Department of Cell BiologyPeking University Health Science CenterBeijingChina
  3. 3.Lake Research Center, Chinese Research Academy of Environmental SciencesBeijing Anwai BeiyuanBeijingChina

Personalised recommendations