Role of the catechol group in the antioxidant and neuroprotective effects of virgin olive oil components in rat brain.

The aim of the present study was to determine the role of the catechol group in the antioxidant and neuroprotective effects of minor components of virgin olive oil in rat brain tissue. Hydroxytyrosol ethyl ether (HT, 2 OH), tyrosol ethyl ether (Ty, 1 OH) and 3,4-di-ortho-methylidene-hydroxytyrosol ethyl ether (MET, no OH) were compared. Oxidative stress was induced with ferrous salts (lipid peroxidation induction), diethylmaleate (depletion of glutathione) and hypoxia-reoxygenation in brain slices. Lipid peroxidation was inhibited in direct proportion to the number of OH groups: HT>Ty>MET. Exposure to HT led to partial recovery of the glutathione system after chemical inhibition or hypoxia-reoxygenation. All three compounds inhibited cell death in hypoxia-reoxygenation experiments (HT≥Ty>MET). Peroxynitrite formation (3-nitrotyrosine) and inflammatory mediators (prostaglandin E2 and interleukin 1ß) were inhibited by all three compounds. In conclusion, the presence of OH groups in the molecule of these phenolic compounds from virgin olive oil is a determinant factor in their antioxidant effect in brain tissue, but this antioxidant effect is not the only explanation for their neuroprotective effect.

Differences in the in vitro antiplatelet effect of dexibuprofen, ibuprofen, and flurbiprofen in human blood.

BACKGROUND: In this study, we compared the in vitro pharmacodynamic profile of dexibuprofen, ibuprofen, and flurbiprofen to identify possible differences in antiplatelet activity. METHODS: In whole blood samples from healthy volunteers, we measured platelet aggregation induced by adenosine diphosphate, collagen and arachidonic acid, platelet thromboxane B(2) (TxB(2)), lipopolysaccharide-induced prostaglandin E(2), leukocyte 6-keto-prostaglandin F(1α) (PGF(1α)), and nitric oxide induced by both constitutive and inducible pathways before and after incubation with increasing concentrations of acetylsalicylic acid, dexibuprofen, ibuprofen, or flurbiprofen. The concentration that inhibited (IC(50)) or increased each variable by 50% was calculated. RESULTS: All 3 drugs inhibited platelet aggregation in a dose-dependent manner, TxB(2), prostaglandin E(2), and 6-keto-PGF(1α), and increased calcium-induced nitric oxide production. Dexibuprofen showed greater antiplatelet potency than ibuprofen and flurbiprofen, and its profile was similar to that of aspirin. For example, IC(50) values for arachidonic acid-induced platelet aggregation were 0.85 ± 0.06 µM for dexibuprofen, 14.76 ± 1.22 µM for ibuprofen, 6.39 ± 0.51 µM for flurbiprofen, and 0.38 ± 0.03 µM for aspirin. All drugs inhibited both thromboxane and prostacyclin synthesis, but the IC(50) anti-TxB(2)/IC(50) anti-6-keto-PGF(1α) ratio was 0.21 ± 0.03 for dexibuprofen, 1.05 ± 0.08 for ibuprofen, 0.79 ± 0.11 for flurbiprofen, and 0.46 ± 0.06 for aspirin. All drugs increased calcium-dependent nitric oxide production. CONCLUSIONS: The aryl propionic acid derivative dexibuprofen was the most potent antiplatelet drug, and its pharmacodynamic profile is similar to aspirin.