Effects of ebselen and N-acetyl cysteine on replicative aging of primary human fibroblast strains

Immunity & Ageing

Table 1 Effect of 30 μM ebselen or 7.5 mM NAC administration in different primary human cell types compared to controls

Human CD4⁺ TCCs	Human CD4⁺ TCCs	Human peripheral blood & CD4⁺ T cells ex vivo (derived from 25–30 or 55–60 year old donors) [3]	MRC-5 (Human embryonic lung fibroblasts)	HFF (Human foreskin fibroblasts)
26 & 45 year old donors [3]	80 year old donors [13]		MRC-5 (Human embryonic lung fibroblasts)	HFF (Human foreskin fibroblasts)
Increase in cumulative PD*	No effect on cumulative PD	Increase in proliferation capacity*	No effect on cumulative PD
Increase in cumulative PD*	No effect on cumulative PD	Increase in proliferation capacity*	No effect on induction of SA – β Gal
Increase in intracellular GSH:GSSG ratio*	No effect on intracellular GSH:GSSG ratio	Increase in intracellular GSH:GSSG ratio*	No effect on induction of cyclin dependent kinase inhibitors (p16, p21)
Decrease in levels of oxidative DNA damage*	No effect in levels of oxidative DNA damage	Decrease in levels of oxidative DNA damage*	Intracellular GSH:GSSG ratio remains unchanged
Decrease in levels of oxidative DNA damage*	No effect in levels of oxidative DNA damage		No significant changes on the levels of oxidative DNA damage
No effect on intracellular total glutathione levels	No effect on intracellular total glutathione levels
No effect on intracellular total glutathione levels	No effect on intracellular total glutathione levels	Increase in intracellular total glutathione levels*	No effect on the increase in phosphorylation of HSP27 with age

The effects of 5 mM NAC administration were similar to 7.5 mM NAC in human peripheral blood and CD⁺ T cells ex vivo irrespective of the age of the donors. 10 μM ebselen or 1.25 mM NAC administration did not have any impact on any of the markers investigated compared to controls in all the cell types and strains. 60 and 100 μM ebselen or 10 mM NAC resulted in inhibition of growth of all the three cell types investigated (Human CD4⁺ TCCs, peripheral blood mononuclear cells and CD4⁺ T cells ex vivo) whereas these concentrations of antioxidants did not have an effect on either of the cell strains (MRC-5 and HFF) compared to controls. All the primary human cell types and strains were maintained in culture in presence of either of the antioxidants throughout their span in culture. *p < 0.05 compared to controls

ISSN: 1742-4933