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The Molecular Mechanisms of Protective Role of Se on the G2/M Phase Arrest of Jejunum Caused by AFB1

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Abstract

Aflatoxin B1 (AFB1) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G2/M cell cycle arrest of broiler’s jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se group) for 21 days, respectively. The histological observation and morphological analysis revealed that 0.4 mg/kg Se prevented the AFB1-associated lesions of jejunum including the shedding of the apical region of villi, the decreased villus height, and villus height/crypt ratio. The cell cycle analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB1-induced G2/M phase arrest in jejunal cells. Moreover, the expressions of ATM, Chk2, p53, Mdm2, p21, PCNA, Cdc25, cyclin B, and Cdc2 analyzed by immunohistochemistry and qRT-PCR demonstrated that 0.4 mg/kg Se restored these parameters to be close to those in the control group. In conclusion, Se promoted cell cycle recovery from the AFB1-induced G2/M phase arrest by the molecular regulation of ATM pathway in the jejunum of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium’s essentiality and its protective roles against AFB1.

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Acknowledgements

This work was supported by the program for Changjiang Scholars and University Innovative Research Team (PCSIRT) (No. 0848) and the Education Department of Sichuan Province (2012FZ0066) and (2013FZ0072).

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Author notes

  1. Jing Fang, Heng Yin, Zhixiang Zheng, and Panpan Zhu contributed equally to this study.

Authors and Affiliations

  1. Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, People’s Republic of China

    Jing Fang, Heng Yin, Zhixiang Zheng, Panpan Zhu, Zhicai Zuo, Hengmin Cui & Junliang Deng

  2. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, People’s Republic of China

    Jing Fang, Heng Yin, Zhixiang Zheng, Panpan Zhu, Zhicai Zuo, Hengmin Cui, Ping Ouyang, Yi Geng & Junliang Deng

  3. College of Life Sciences, China West Normal University, Nanchong, 637002, Sichuan, People’s Republic of China

    Xi Peng

  4. Life Science Department, Sichuan Agricultural University, Ya’an, Sichuan, People’s Republic of China

    Yi Zhou

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  1. Jing Fang
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Correspondence to Xi Peng or Zhicai Zuo.

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The use of broilers and all experimental procedures involving animals were approved by Sichuan Agricultural University Animal Care and Use Committee. Nutritional requirements were adequate according to National Research Council (1994) (National Research Council, 1994) [30] and Chinese Feeding Standard of Chicken (NY/T33-2004).

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Fang, J., Yin, H., Zheng, Z. et al. The Molecular Mechanisms of Protective Role of Se on the G2/M Phase Arrest of Jejunum Caused by AFB1 . Biol Trace Elem Res 181, 142–153 (2018). https://doi.org/10.1007/s12011-017-1030-2

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