Hydroxytyrosol and its sulfate metabolites protect enterocyte-like cells against the oxidized cholesterol pro-oxidant effect

Abstract

Hydroxytyrosol (HT) is a phenolic alcohol present in extravirgin olive oil, where it exists in simple form or as conjugates. HT is absorbed and extensively metabolized at intestinal level, resulting in sulfated and glucuronidated metabolites. The aim of this study was to investigate the ability of the sulfate metabolites of HT (HT-S) to act as antioxidants counteracting the pro-oxidant effect of oxidized cholesterol in intestinal cells. For this purpose, we synthesized HT-S using a chemical methodology and examined their antioxidant activity in Caco-2 monolayers in comparison with the parent compound. Exposure to oxidized cholesterol led to ROS production, oxidative damage, as indicated by the MDA increase, a decrease of reduced glutathione level and an enhancement of glutathione peroxidase activity. HT and HT-S were able to counteract the action of oxidized cholesterol; HT-S showed an efficiency in protecting intestinal cells comparable to that of the parent compound, strengthening the assumption that the potential beneficial effect of the parent compounds is retained, although extensive metabolisation occurs, the resulting metabolites being able to exert a biological action themselves.