Mercury Chloride Affects Band 3 Protein-Mediated Anionic Transport in Red Blood Cells: Role of Oxidative Stress and Protective Effect of Olive Oil Polyphenols

Abstract

Mercury is a toxic heavy metal widely dispersed in the natural environment. Mercury exposure induces an increase in oxidative stress in red blood cells (RBCs) through the production of reactive species and alteration of the endogenous antioxidant defense system. Recently, among various natural antioxidants, the polyphenols from extra-virgin olive oil (EVOO), an important element of the Mediterranean diet, have generated growing interest. Here, we examined the potential protective effects of hydroxytyrosol (HT) and/or homovanillyl alcohol (HVA) on an oxidative stress model represented by human RBCs treated with HgCl2 (10 µM, 4 h of incubation). Morphological changes as well as markers of oxidative stress, including thiobarbituric acid reactive substance (TBARS) levels, the oxidation of protein sulfhydryl (-SH) groups, methemoglobin formation (% MetHb), apoptotic cells, a reduced glutathione/oxidized glutathione ratio, Band 3 protein (B3p) content, and anion exchange capability through B3p were analyzed in RBCs treated with HgCl2 with or without 10 μM HT and/or HVA pre-treatment for 15 min. Our data show that 10 µM HT and/or HVA pre-incubation impaired both acanthocytes formation, due to 10 µM HgCl2, and mercury-induced oxidative stress injury and, moreover, restored the endogenous antioxidant system. Interestingly, HgCl2 treatment was associated with a decrease in the rate constant for SO42− uptake through B3p as well as MetHb formation. Both alterations were attenuated by pre-treatment with HT and/or HVA. These findings provide mechanistic insights into benefits deriving from the use of naturally occurring polyphenols against oxidative stress induced by HgCl2 on RBCs. Thus, dietary supplementation with polyphenols might be useful in populations exposed to HgCl2 poisoning.

The Bioactivity of a Hydroxytyrosol-Enriched Extract Originated after Direct Hydrolysis of Olive Leaves from Greek Cultivars

“…The strong protective activity of HT is also displayed against heavy metal-caused damage. More specifically, HT prevented mercury-induced oxidative stress at red blood cells (RBCs) [ 24 ], as well as protecting the rat brain from arsenic (As)-induced oxidative stress [ 25 ]. HΤ is generally recognized as safe (GRAS) by the European Food Safety Authority (EFSA) and the Food and Drug Administration (FDA) and is asserted to improve human health when consumed at a minimum dose of 5 mg per day, as described in EU Regulation 432/2012 [ 26 ].…”

Effect of Nutraceutical Factors on Hepatic Intermediary Metabolism in Wistar Rats with Induced Tendinopathy

“…HT has been shown to prevent cytokine formation, nitric oxide (NO) generation, tumor necrosis factor-alpha (TNF-α) secretion, and mRNA expression and to inhibit the expression of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Some research has shown that HT treatment prevents acanthocyte formation observed after HgCl 2 exposure and prevents HgCl 2 induced oxidative stress damage, including ROS production, lipid peroxidation, and oxidation of the sulfhydryl group of total proteins in the plasma membrane [ 16 ].…”

Aging Injury Impairs Structural Properties and Cell Signaling in Human Red Blood Cells; Açaì Berry Is a Keystone

“…To fulfill their tasks, RBCs are capable of elastically deforming during mechanical stress and pass via the narrow microcirculation capillaries [ 19 , 20 ]. There is compelling evidence that treatment of RBCs with oxidizing compounds not only impair their deformability but also change their shape, thus suggesting a key role of intracellular redox status, both in structural characteristics and the control of deformability [ 21 , 22 , 23 , 24 , 25 , 26 ]. Surprisingly, a close relationship between oxidative stress and RBC deformability has also been reported in experimental investigations involving patients with sickle cell disease.…”