Six-day selenium supplementation led to either UVA-photoprotection or toxic effects in human fibroblasts depending on the chemical form and dose of Se.

Selenium (Se) is an essential trace element with a narrow safety zone and unclear effects on skin photoageing. The aim of this work was to investigate the photoageing properties of sodium selenite or selenomethionine (SeMet) after a long term (6 days) Se supplementation in normal human skin fibroblasts (NHSF) subjected to ultraviolet-A (UVA) irradiation inducing 30% cell death. The uptake, toxicity and antioxidant effects of sodium selenite and SeMet were compared to better understand their photoageing properties. SeMet uptake was better than sodium selenite and their uptake by fibroblasts was not via an actively transport process. Sodium selenite induced a higher toxicity than SeMet. At 5 µM, sodium selenite inhibited cell proliferation associated with a blockage in the G2 phase and induced DNA fragmentation leading to caspase-3-dependent apoptosis cell death. At low doses (<1 µM), SeMet and sodium selenite induced glutathione peroxidase-1 (GPX1) activity and selenoproteinW1 (SEPW1) transcript expression but metalloproteinase (MMP)-1 was only induced by sodium selenite. SeMet and sodium selenite did not protect NHSFs from UVA-induced cell death. However, SeMet decreased malondialdehyde (MDA) and protected NHSFs from UVA-induced MMP1 and MMP3. We then observed a large difference in terms of photoprotection according to selenium forms. SeMet may be a potential agent for the prevention and treatment of skin photoageing.

Long-term selenium supplementation in HaCaT cells: importance of chemical form for antagonist (protective versus toxic) activities.

The beneficial effect of selenium (Se) on cancer is known to depend on the chemical form, the dose and the duration of the supplementation. The aim of this work was to explore long term antagonist (antioxidant versus toxic) effects of an inorganic (sodium selenite, Na2SeO3) and an organic (seleno-L-methionine, SeMet) forms in human immortalized keratinocytes HaCaT cells. HaCaT cells were supplemented with Na2SeO3 or SeMet at micromolar concentrations for 144 h, followed or not by UVA radiation. Se absorption, effects of UVA radiation, cell morphology, antioxidant profile, cell cycle processing, DNA fragmentation, cell death triggered and caspase-3 activity were determined. At non-toxic doses (10 µM SeMet and 1 µM Na2SeO3), SeMet was better absorbed than Na2SeO3. The protection of HaCaT from UVA-induced cell death was observed only with SeMet despite both forms increased glutathione peroxidase-1 (GPX1) activities and selenoprotein-1 (SEPW1) transcript expression. After UVA irradiation, malondialdehyde (MDA) and SH groups were not modulated whatever Se chemical form. At toxic doses (100 µM SeMet and 5 µM Na2SeO3), Na2SeO3 and SeMet inhibited cell proliferation associated with S-G2 blockage and DNA fragmentation leading to apoptosis caspase-3 dependant. SeMet only led to hydrogen peroxide production and to a decrease in mitochondrial transmembrane potential. Our study of the effects of selenium on HaCaT cells reaffirm the necessity to take into account the chemical form in experimental and intervention studies.