Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: Possible involvement of the glutathione pathway

- Hydroxytyrosol prevents the mercury(Hg)-induced suicidal death in red blood cells.
- Hydroxytyrosol prevents the Hg-induced phosphatidylserine exposure at the cell surface.
- Hydroxytyrosol counteracts the Hg-induced decrease in intracellular ATP levels.
- Hydroxytyrosol counteracts the Hg-induced glutathione depletion.
- Hydroxytyrosol does not affect the Hg-induced Ca2+ influx and decrease in cell volume.

Hydroxytyrosol (HT) is a phenolic antioxidant naturally occurring in virgin olive oil. In this study, we investigated the possible protective effects of HT on programmed suicidal death (eryptosis) induced by mercury (Hg) treatment in intact human erythrocytes (RBC). Our study confirms that the Hg-eryptosis is characterized by phosphatidylserine (PS) exposure at the cell surface, with cell shrinkage and ATP and glutathione depletion; calcium influx is also a key event that triggers eryptosis. Here we report that cell preconditioning with an optimal dose (1-5 μM) of HT prior to exposure to 2.5 μM HgCl2 causes a noteworthy decrease in PS-exposing RBC, almost restoring ATP and GSH content. Conversely, HT shows no effect against decrease in cell volume nor against influx of extracellular calcium. Taken together our data provide the first experimental evidence of the efficacy of HT in modulating the programmed suicidal death in non nucleated cells; the reported findings also confirm that the prevention of Hg toxicity should be regarded as an additional mechanism responsible for the health-promoting potential of this dietary phenol. Finally, virgin olive oil would appear to be a promising healthy food to reduce the adverse effects of chronic mercury exposure in humans.