Gender Differences in the Antioxidant Response of Oral Administration of Hydroxytyrosol and Oleuropein Against N-ethyl-N-nitrosourea (Enu)-Induced Glioma

Brain tumorigenesis has been associated not only with oxidative stress, but also with a reduced response of non-enzyme and enzyme antioxidant defense systems. In fact, the imbalance between free-radical production and the efficiency of the antioxidant defense systems triggers the process because the central nervous system (CNS) is very sensitive to free-radical damage. Phenolic compounds, mainly oleuropein and its major metabolite hydroxytyrosol, derived from olives and virgin olive oil, have been shown to exert important anticancer activities both in vitro and in vivo due to their antioxidant properties. The present study analyzes the effects of the oral administration of oleuropein, hydroxytyrosol and the mixture of both phenolic compounds in rats with transplacental N-ethyl-N-nitrosourea (ENU)-induced brain tumors to analyze their potential effect against brain tumorigenesis through the modification of redox system components. Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems and blood chemistry were assayed in the different experimental groups. The treatment with oleuropein, hydroxytyrosol and/or the mixture of both phenolic compounds promotes a limited beneficial effect as anticancer compounds in our ENU-induced animal model of brain tumor. These effects occur via redox control mechanisms involving endogenous enzymatic and non-enzymatic antioxidant defense systems, and are highly dependent on the gender of the animals.