Effect of olive oil minor components on oxidative stress and arachidonic acid mobilization and metabolism by macrophages RAW 264.7

Minor components of virgin olive oil may explain the healthy effects of the Mediterranean diet on the cardiovascular system and cancer development. The uncontrolled production of reactive oxygen species (ROS) and arachidonic acid (AA) metabolites contributes to the pathogenesis of cardiovascular disease and cancer, and inflammatory cells infiltrated in the atheroma plaque or tumor are a major source of ROS and eicosanoids. We aimed to determine the effects of squalene, beta-sitosterol, and tyrosol, which are representative of the hydrocarbons, sterols, and polyphenols of olive oil, respectively, on superoxide anion (O-2(-)), hydrogen peroxide (H2O2), and nitric oxide ((NO)-N-.) levels. We also studied AA release and eicosanoid production by phorbol esters (PMA)-stimulated macrophages RAW 264.7. beta-Sitosterol and tyrosol decreased the O-2(-) and H2O2 production induced by PMA, and tyrosol scavenged the O-2(-) released by a ROS generating system. These effects were correlated with the impairment of [H-3]AA release, cyclooxygenase-2 (COX-2) expression, and prostaglandin E-2/leukotriene B-4 synthesis in RAW 264.7 cultures stimulated by PMA. beta-Sitosterol exerted its effects after 3-6 h of preincubation. Tyrosol inhibited the [H-3]AA release induced by exogenous ROS. beta-Sitosterol and tyrosol also reduced the (NO)-N-. release induced by PMA, which was correlated with the impairment of inducible nitric oxide synthase (iNOS) levels. This may be correlated with the modulation of NF-kappaB activation. Further studies are required to gain more insight into the potential healthy effects of minor components of extra virgin olive oil. (C) 2003 Elsevier Inc.