Effects of Hydroxytyrosol on Cyclosporine Nephrotoxicity

Olive oil represents the typical lipidic source of the Mediterranean diet that has been associated with a low incidence of several pathologies, including cardiovascular diseases and neurological disorders. The beneficial properties of olive oil have been mainly attributed to its high content of monounsaturated oleic acid; however, in recent years converging evidence indicates that the non-glyceride fraction of olive oil, rich in vitamin and non-vitamin antioxidants including polyphenols, significantly contributes to its benefits on human health. Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET) is the main ortho-diphenolic compound of olive oil and is mainly responsible for the antioxidant properties of this nutrient. Indeed, it has been shown to function as an efficient scavenger of peroxyl radicals in several biological systems and contributes to increase the shelf life of the oil, preventing its auto-oxidation. DOPET inhibits in vitro low-density lipoprotein oxidation and modulates the oxidative/antioxidative balance in plasma. Experiments in the present study demonstrate that DOPET, which effectively permeates cell membranes via passive diffusion, counteracts the cytotoxic effects of reactive oxygen species (ROS) in various human systems. Preincubation of intestinal Caco-2 cells with DOPET prevents the typical damages of oxidative stress. Similarly, this polyphenol exerts a protective effect against the H2O2-induced oxidative hemolysis and lipid peroxidation in red blood cells.