Research Papers:

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs

Hongjing Zhao, Ying He, Siwen Li, Xiao Sun, Yu Wang, Yizhi Shao, Zhijun Hou and Mingwei Xing _

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Oncotarget. 2017; 8:40327-40344. https://doi.org/10.18632/oncotarget.16960

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Hongjing Zhao1,*, Ying He1,*, Siwen Li1, Xiao Sun1, Yu Wang1, Yizhi Shao1, Zhijun Hou1 and Mingwei Xing1

1Department of Physiology, College of Wildlife Resources, Northeast Forestry University, Harbin 150040, Heilongjiang, PR China

*These authors contributed equally to this work

Correspondence to:

Mingwei Xing, email: [email protected]

Zhijun Hou, email: [email protected]

Keywords: arsenic, apoptosis, oxidative stress, inflammation, chicken

Received: February 01, 2017     Accepted: March 29, 2017     Published: April 08, 2017


In many organ dysfunctions, arsenic and its compounds are well known to induce apoptosis by the mitochondria and death receptor apoptotic pathways in liver and airway. However, it is less reported that which signaling pathways contribute to excessive apoptosis of chicken immune organs, a major target of toxic metals biotransformation, which suffer from subchronic arsenism. In this study, we investigated whether the mitochondria or death receptor apoptotic pathways activated in the immune organs (spleen, thymus and bursa of Fabricius) of one-day-old male Hy-line chickens exposed to arsenic trioxide (As2O3), which were fed on diets supplemented with 0, 0.625, 1.25 and 2.5 mg/kg BW of As2O3 for 30, 60 and 90 days. We found that (1) Oxidative damage and inflammatory response were confirmed in the immune organs of chickens fed on As2O3 diet. (2) Subchronic arsenism induced typical apoptotic changes in ultrastructure. (3) TdT-mediated dUTP Nick-End Labeling (TUNEL) showed that the number of apoptotic cells significantly increased under subchronic arsenism. (4) As2O3-induced apoptosis of immune organs involved in mitochondrial pathway (decrease of B-cell lymphoma-2 (Bcl-2) and increase of protein 53 (p53), Bcl-2 Associated X Protein (Bax), caspase-9, caspase-3) and death receptor pathway (increase of factor associated suicide (Fas) and caspase-8). In conclusion, this work is the first to demonstrate that the activation of mitochondria and death receptor apoptosis pathways can lead to excessive apoptosis in immune organs of chickens, which suffer from subchronic arsenism, meanwhile, oxidative stress as well as subsequent inflammatory is a crucial driver of apoptosis.

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