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. 2018 Apr 12:2018:9042192.
doi: 10.1155/2018/9042192. eCollection 2018.

Comparative Analysis of the Effects of Olive Oil Hydroxytyrosol and Its 5- S-Lipoyl Conjugate in Protecting Human Erythrocytes from Mercury Toxicity

Arbace Officioso  1 , Lucia Panzella  2 , Fabiana Tortora  1 , Maria Laura Alfieri  2 , Alessandra Napolitano  2 , Caterina Manna  1
Affiliations

Comparative Analysis of the Effects of Olive Oil Hydroxytyrosol and Its 5- S-Lipoyl Conjugate in Protecting Human Erythrocytes from Mercury Toxicity

Arbace Officioso et al. Oxid Med Cell Longev. .

Abstract

Oxidative stress is one of the underlying mechanisms of the toxic effects exerted by mercury (Hg) on human health. Several antioxidant compounds, including the olive oil phenol hydroxytyrosol (HT), were investigated for their protective action. Recently, we have reported that 5-S-lipoylhydroxytyrosol (Lipo-HT) has shown increased antioxidant activities compared to HT and exerted potent protective effects against reactive oxygen species (ROS) generation and oxidative damage in human hepatocellular carcinoma HepG2 cell lines. In this study, the effects of Lipo-HT and HT on oxidative alterations of human erythrocytes induced by exposure to 40 μM HgCl2 were comparatively evaluated. When administered to the cells, Lipo-HT (5-20 μM) proved nontoxic and it decreased the Hg-induced generation of ROS, the hemolysis, and the depletion of intracellular GSH levels. At all tested concentrations, Lipo-HT exhibited higher ability to counteract Hg-induced cytotoxicity compared to HT. Model studies indicated the formation of a mercury complex at the SH group of Lipo-HT followed by a redox reaction that would spare intracellular GSH. Thus, the enhanced erythrocyte protective action of Lipo-HT from Hg-induced damage with respect to HT is likely due to an effective chelating and reducing ability toward mercury ions. These findings encourage the use of Lipo-HT in nutraceutical strategies to contrast heavy metal toxicity in humans.

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Figures

Figure 1
Figure 1
Figure 2
Figure 2
Effect of HT and Lipo-HT on Hg-induced hemolysis. Cells were treated with HgCl2 at 40 μM for 24 h in the presence of increasing concentrations of the selected compounds. Data are the means ± SE (n = 9). Statistical analysis was performed with one-way ANOVA followed by Dunnett's test (p < 0.05). Means with different letters are significantly different.
Figure 3
Figure 3
Effect of HT and Lipo-HT on Hg-induced ROS production in RBC. Cells were treated with HgCl2 at 40 μM for 4 h in the presence of increasing concentrations of the selected compounds. ROS production was evaluated by means of the fluorescent probe DCF. Data are the means ± SE (n = 9). Statistical analysis was performed with one-way ANOVA followed by Dunnett's test (p < 0.05). Means with different letters are significantly different.
Figure 4
Figure 4
Effect of HT and Lipo-HT on Hg-induced GSH decrease in RBC. Cells were treated with 40 μM HgCl2 for 4 h in the presence of increasing concentrations of the selected compounds. Data are the means ± SE (n = 9). Statistical analysis was performed with one-way ANOVA followed by Dunnett's test (p < 0.05). Means with different letters are significantly different.
Figure 5
Figure 5
Analysis of the reaction mixture of Lipo-HT with Hg2+ ions at pH 7.4. (a) Total ion current (TIC) chromatograms of the reaction mixture of Lipo-HT (50 μM) with Hg2+ (100 μM) at pH 7.4 (top: before addition of Hg2+, bottom: 5 min after addition of Hg2+). (b) Top: MS spectrum of the product eluted at 25 min; bottom: inset showing the Hg isotopic signatures of the complex. (c) MS spectrum of the product eluted at 22 min.
Figure 6
Figure 6
Mechanism proposed for the reaction of Lipo-HT with Hg2+ at pH 7.4.
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