Environmental Science and Pollution Research

, Volume 25, Issue 16, pp 15462–15473 | Cite as

Alterations of antioxidant indexes and inflammatory cytokine expression aggravated hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in Gallus gallus exposed to arsenic and copper

  • Juanjuan Liu
  • Hongjing Zhao
  • Yu Wang
  • Yizhi Shao
  • Jinglun Li
  • Mingwei Xing
Research Article


In this study, we sought to investigate the effects of sub-chronic exposure of arsenic (As) and copper (Cu) on oxidative stress, inflammatory response, and mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two 1-day-old male Hy-line chickens were treated with basal diet, 30 mg/kg arsenic trioxide (As2O3), or/and 300 mg/kg copper sulfate (CuSO4) for 4, 8, and 12 weeks. Study revealed that exposure to As or/and Cu undermined the antioxidant function and increased lipid peroxidation. Worse yet, liver cell swollen, vacuolar degeneration, and inflammatory cell infiltration were accompanied by an increase of the nuclear factor-κB (NF-κB) and its downstream inflammation-related genes after exposure to As or/and Cu. Furthermore, mitochondria swollen and chromatin condensation were found in As and Cu groups, and hepatocyte nuclear membrane rupture and markedly increased (P < 0.01) apoptosis index were observed in As combined with Cu group. Meanwhile, the transcription and protein expression levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c), and caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated in As, Cu, and As + Cu groups in the liver tissues (P < 0.05, P < 0.01). Our results indicated that exposure to As or/and Cu could lead to oxidative stress, inflammatory response, and tissue damage and aggravate hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in chicken liver. And As and Cu showed a possible synergistic relationship in liver damage.


Chicken liver Arsenic Copper Oxidative stress Inflammation Apoptosis 


Funding information

This study was supported by the National Natural Science Foundation of China (Grant No.31672619), the Fundamental Research Funds for the Central Universities (Grant No. 2572016EAJ5), and the Natural Science Foundation of Heilongjiang Province (Grant No. C2015061).

Compliance with ethical standards

Animal care and all experimental procedures were done according to the guidelines of the Institutional Animal Care and Use Committee of Northeast Forestry University (approval no. UT-31; June 20, 2014).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Juanjuan Liu
    • 1
  • Hongjing Zhao
    • 1
  • Yu Wang
    • 1
  • Yizhi Shao
    • 1
  • Jinglun Li
    • 1
  • Mingwei Xing
    • 1
  1. 1.Department of Physiology, College of Wildlife ResourcesNortheast Forestry UniversityHarbinPeople’s Republic of China

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