0294 : Glucuronide metabolites of hydroxytyrosol are responsible for the antioxidative properties of olive oil

Abstract

Hydroxytyrosol (HT) is known to be a strong polyphenolic antioxidant of olive oil. However, its in vivo effects are controversial since intestinal absorption is low and it is highly metabolized into glucuronides (GC), suggesting that these metabolites could be responsible of HT biological activity in vivo . Our objectives were to study the direct effects of HT and its glucuronides on vascular function and the oxidative stress vascular protection on healthy and diabetic rats The vascular function was assessed on aortas from diabetic-High Fat Sucrose diet (HFS) and age-matched (22 weeks) control fed with a standard diet (SD) Wistar rats, in comparison to young (9 weeks) control Wistar rats (ySD). The endothelium-dependent and independent vasorelaxing effects of these compounds were assessed via incremental doses of HT and GC (10 -9 to 10 -4 M) and compared to Resveratrol (Res). Expression and phosphorylation of Ser 1177 eNOS were measured by Western blot. To evaluate the anti-oxidative effects of these polyphenols (100 μM, 5min), vascular function was assessed in presence/absence of t -BOOH (500μM, 30min). HT and GC did not show any endothelium-dependent and independent vasorelaxation effects in ySD and HFS rats while Res produced vasorelaxing effect at 10 -4 M in all groups of rats and no vasorelaxant effects were noticed in SD rats. The overall absence of vasorelaxing effect can be explained by the lack eNOS phosphorylation. As for the antioxidative properties, HT, GC and Res increased significantly endothelium-dependent relaxation in comparison of aorta rings treated only with t -BOOH (79.9%±9.2, 74.1%±8.6, 71.0%±8.2, 48.4%±5.3 respectively). In addition, co-incubation of HT/GC and Res/GC increased even more the vasorelaxation under pro-oxydant conditions. In diabetic HFS rats, (i) the incubation for 5min with HT and GC did not improve neither vasorelaxation nor the contraction; (ii) however, a prolonged 30 min incubation resulted in more pronounced and significant contractile (64.8%±12.4 and 95.6%±16.3, respectively) and endothelium-dependent relaxation effects (30%±7.5 and 58.1%±10.3 respectively) for GC in comparison to HT. In conclusion, GC seems to be responsible for the anti-oxidative properties of olive oil but further experimentations have to be realized concerning its possible interconversion in HT by β-glucuronidase. The author hereby declares no conflict of interest