An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells
Open accessAbstract
Background: The research literature has documented age-related increases in genetic damage, including oxidative DNA damage, in human T lymphocytes, in vitro and ex vivo. Such damage has the potential to interfere with the ability of the T cells to proliferate at times when they need to, such as when antigen challenged. The consequence of this could be a sub-optimal immune response in vivo. Context and purpose: The purpose of the research reported in this paper was to investigate the impact of two antioxidants, which can be administered in vivo, Ebselen and N-acetyl L-cysteine, on the age-related increase in genetic damage, and on T cell proliferation and lifespan. In vitro human T cell clones, ex vivo peripheral blood mononuclear cells or T cells were supplemented with different concentrations of antioxidants, under standard conditions and for different periods of time. A range of assays were then applied in order to determine any impact of the antioxidants. Results: 30 μM ebselen or 7.5 mM N-acetyl L-cysteine supplementation resulted in a significantly higher intracellular GSH: GSSG ratio. This increased ratio was accompanied by reduced levels of oxidative DNA damage in established CD4+ human T cell clones, from a young or a middle-aged donor. Additionally, cultures of primary human peripheral blood mononuclear cells and CD4+ T cells from donors aged 25–30 or 55–60 years were also supplemented with these agents. Cells from all sources exhibited increased proliferation, and in the case of the T cell clones, an increase in cumulative population doublings. Neither ebselen nor N-acetyl L-cysteine had such effects on clones supplemented from the midpoint of their in vitro lifespan. Conclusions: Ebselen and N-acetyl L-cysteine, under certain conditions, may have anti-immunosenescent potential in T cells in in vitro clonal and ex vivo polyclonal culture models.
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Antioxidants Ebselen and N-acetyl-cysteine increase the lifespan and proliferative capacity of CD4+ T cell clones from healthy young and middle-aged donors, with increased GSH/GSSG ratio and lower oxidative DNA damage.
“Supplementing cultures with these antioxidants substantially increased the lifespan and proliferative capacity of T cell clones, which occurred in parallel with an increase in the ratio of reduced glutathione (GSH) to oxidised glutathione (GSSG) and lower oxidative DNA damage (Marthandan et al. 2013).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Marthandan et al. 2013
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- Ji L Jun-Jie C Fang Z Cui Z Ebselen protection against hydrogen peroxide induced cytotoxicity and DNA damage in HL-60 cells Acta Pharmacol Sin 2000 21 5 455 459 11324446
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Is immunosenescence influenced by our lifetime “dose” of exercise?
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- Authors
- Marthandan, S., Hyland, P., Pawelec, G., & Barnett, Y.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- National Blood Authority (AU)
- University of Tübingen (DE)
- Nottingham Trent University (GB)
- Corresponding author
- Barnett, Yvonne
- Venue
- Immunity & Ageing
- Published
- 2013-02-21
- Volume
- 10
- Issue
- 1
- Pages
- 7-7
- ISSN
- 1742-4933 (ISSN-L)
- PMC
- PMC3610132
- OpenAlex
- W1597804198
- Cited by
- 16
- References
- 27
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Immunity & Ageing (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Anglia Ruskin Research Online (Anglia Ruskin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Funders
- University of Sussex
- Medical Research Council
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- ebselen, N-acetylcysteine, antioxidants, immunosenescence, T cell senescence, oxidative DNA damage, glutathione, T cell proliferation, CD4+ T cells, T cell lifespan, peripheral blood mononuclear cells
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