Modulation of the superoxide anion production and MMP-9 expression in PMA stimulated THP-1 cells by olive oil minor components: Tyrosol and hydroxytyrosol

Extra virgin olive oil has been associated with a reduced incidence of risk factors for coronary heart disease also owing to the presence of antioxidant biophenols. Reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) have been implicated in numerous somatic illnesses, including cardiovascular disorders and cancer. The aim of this work was to study the capacity of virgin olive oil tyrosol (T) and hydroxytyrosol (HT) at impairing superoxide production and MMP-9 expressions in monocyte cells (THP-1) conveniently differentiated into adherent macrophages, taken as a model of human macrophages implicated in atheroma.O2− production was evaluated in THP-1 cells by using lucigenin as a specific chemiluminescent probe. Cells, after differentiation for 72 h, were preincubated in the presence of HT and T at increasing concentrations for 4, 15 and 24 h, and then, monocyte-like cells were stimulated by phorbol myristate acetate (PMA) and the O2−-dependent luminescence was immediately recorded at 37 °C by means of a Luminometer. Enzymatic activity of MMP-9 derived from a medium of cells preincubated, or not, with T or HT was tested by zymography.As compared to the cells without treatment, cells preincubated with HT, showed a decrease of O2− production (50%) at 1 μM for 15 h of preincubation time. Tyrosol fully prevented ROS overproduction at 15 h and, like HT displayed a high degree of protection but at higher concentrations and later time points (24 h). Gelatin zymograms revealed a reduction of the expression of MMP-9 in conditioned medium derived from T and HT-treated cells. These findings give further evidence in favour of olive oil consumption to counteract cardiovascular diseases.