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Biochemistry (Moscow)

, Volume 84, Issue 6, pp 617–626 | Cite as

Defective Central Immune Tolerance Induced by High-Dose D-Galactose Resembles Aging

  • H. M. Du
  • Y. J. Wang
  • X. Liu
  • S. L. Wang
  • S. M. Wu
  • Z. Yuan
  • X. K. ZhuEmail author
Article
  • 1 Downloads

Abstract

D-Galactose (D-Gal) promotes accumulation of reactive oxygen species and formation of advanced glycation end-products, ultimately resulting in oxidative stress. D-Gal has been widely used to induce accelerated aging in anti-aging medical research. Although thymic epithelial cells are particularly sensitive to oxidative stress, there are few reports on the thymus changes accompanying D-Gal-induced aging in mice. To study the effect of D-Gal on rodent thymus, we investigated the degree of thymus atrophy and changes in the atrophy relative index in C57BL/6J mice following subcutaneous injection of D-Gal at different doses (200, 500, 1000 mg/kg per day) for 60 days. Compared with the vehicle-treated (0.9% saline) and young controls, D-Gal at doses of 500 and 1000 mg/kg per day led to a significant thymic atrophy; the latter dose caused atrophy similar to that observed in naturally aged (18-20-month-old) mice. Mice treated with high-dose D-Gal exhibited greater immunosenescence, defective central immune tolerance, increased levels of activated splenic immune cell, and chronic low-grade inflammation, i.e., outcomes similar to those observed in natural aging in mice. Taken together, our results indicate that mice treated with high-dose D-Gal may be a valid model for studying induced thymic atrophy and effects of aging on the immune system.

Keywords

D-galactose oxidative stress thymic aging central immune tolerance negative selection 

Abbreviations

D-Gal

D-galactose

MDA

malondialdehyde

NS

normal saline

ROS

reactive oxygen species

RTE

recent thymic emigrant

SAMP

senescence-accelerated mouse prone (model)

SOD

superoxide dismutase

TEC

thymic epithelial cell

TRA

tissue-restricted antigen

tTreg

thymic regulatory T cell

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Notes

Acknowledgements

The authors wish to thank the International Science Editing (http://www.international-scienceediting.com) for their assistance in the preparation of this manuscript.

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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • H. M. Du
    • 1
    • 2
  • Y. J. Wang
    • 1
  • X. Liu
    • 1
  • S. L. Wang
    • 2
  • S. M. Wu
    • 3
  • Z. Yuan
    • 3
  • X. K. Zhu
    • 1
    Email author
  1. 1.Research CenterShengjing Hospital of China Medical University, Economic Development ZoneBenxiChina
  2. 2.Department of OncologyShengjing Hospital of China Medical UniversityShenyangChina
  3. 3.Department of Blood TransfusionShengjing Hospital of China Medical UniversityShenyangChina

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