Hydroxytyrosol and tyrosol sulfate metabolites protect against the oxidized cholesterol pro-oxidant effect in Caco-2 human enterocyte-like cells

Abstract

The aim of this study was to investigate the ability of the sulfate metabolites of hydroxytyrosol (HT) and tyrosol (TYR) to act as antioxidants counteracting the pro-oxidant effect of oxidized cholesterol in intestinal cells. For this purpose, we synthesized sulfate metabolites of HT and TYR using a chemical methodology and examined their antioxidant activity in Caco-2 monolayers in comparison with the parent compounds. Exposure to oxidized cholesterol led to ROS production, oxidative damage, as indicated by the MDA increase, a decrease of reduced glutathione concentration and an enhancement of glutathione peroxidase activity. All the tested compounds were able to counteract the oxidizing action of oxidized cholesterol; HT and TYR sulfate metabolites showed an efficiency in protecting intestinal cells comparable to that of the parent compounds, 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.

Antioxidant Effect of Natural Table Olives Phenolic Extract Against Oxidative Stress and Membrane Damage in Enterocyte‐Like Cells

“…It is the only phenol that has been recognized by the European Food Safety Authority with a protective activity on blood lipids from oxidative damage, when consumed daily within a balanced diet (EFSA ). A protective role of hydroxytyrosol against alteration of redox status and membrane oxidative damage in Caco‐2 cells has been reported (Deiana and others ; Atzeri and others ). Hydroxytyrosol may permeate Caco‐2 membranes (Corona and others ), thus its protective role may be exerted both inside and outside the cell.…”

“…ROS production in Caco‐2 cells was determined using the fluorescent probe H 2 ‐DCF‐DA, according to Atzeri and others (Atzeri and others ), with minor modifications. Cells, grown and differentiated in 96‐well plates, were incubated with 10 μM of H 2 ‐DCF‐DA in 100 μL of PBS for 30 min.…”

“…Cells were then scraped into 200 μL of ice‐cold PBS and centrifuged at 10000 g for 20 min at 4 °C. The pellet was used to determine GSH level through EC‐HPLC quantification (Agilent 1260 infinity coupled with an electrochemical detector DECADE II Antec, Leyden, Netherlands) (Atzeri and others ).…”

Modulation of intestinal epithelium homeostasis by extra virgin olive oil phenolic compounds

“…However, this hypothesis has never been proven in humans; indeed, a pilot study on humans demonstrated that HT administration did not significantly modify phase II enzyme expression in peripheral blood mononuclear cells. 99 Recent studies showed the ability of TYR and its sulfate metabolite to induce the GPx activity in Caco-2 cells 87 and, together with its glucuronide metabolite, to restore the GSH level and related antioxidant enzymes in TNF-α treated human endothelial cells, 100 as previously demonstrated in macrophages, where TYR preserved cellular antioxidant defenses against the pro-oxidant effect of oxidized LDL. 101 In a mouse model of lipopolysaccharide (LPS)-induced acute lung injury, TYR pretreatment attenuated the inflammatory response and improved the expression of the antioxidant enzymes, through the activation of Nrf2.…”

“…HT has been recognized as the most efficient free radical scavenger and radical chain breaker, and its catecholic structure is also able to prevent reactive species formation through metal chelation features. 82,83 It has been shown to protect Caco-2 cells against oxidative injury, 84-86 because of its scavenging properties, and its major metabolites, sulfates and glucuronides, showed an efficiency in protecting Caco-2 cells, 87 as well as renal cells 88 and erythrocytes, 89 comparable to or even better than that of the parent compound. TYR has also been shown to be effective in protecting Caco-2 cells against the cytostatic and cytotoxic effects produced by oxidized LDL 90 and to possess scavenging effects on peroxyl radicals, 84 93 Although there are no studies specifically regarding the intestinal compartment, trials in animal models and cell cultures demonstrated that HT is able to increase the endogenous defense system, through the modulation of related gene expression.…”