S15 (II) Mercury and selenium interactions: Biogeochemistry and human health

It is well known that an antagonistic effect exists between selenium (Se) and mercury (Hg), and that Se can play a protective role against Hg toxicity in organisms. In order to find an evidence for such connection, total Hg and Se were determined in 1654 umbilical cord blood samples, 1081 maternal blood samples, and 1051 breast milk samples in pregnant women from Slovenia, Croatia, Italy and Greece. Methyl mercury (MeHg) was determined in a subset of samples (468 umbilical cord blood samples, 364 maternal blood samples, and 268 breast milk samples). The study was part of a research project within the EU 6^th framework programme Public health impact of long-term low-level mixed element exposure in susceptible population strata (PHIME). Total Hg and Se levels in cord blood of Slovenian women (Med 1.52 ng/g and 76 ng/g, respectively) were significantly lower compared to the levels in women from Croatia (Med 2.94 ng/g and 96 ng/g, respectively), Italy (Med 3.94 ng/g and 113 ng/g, respectively) and Greece (Med 5.81 ng/g and 104 ng/g, respectively). Total Hg levels in women from Greece were significantly higher than the levels in women from other countries, while the Se levels were the highest in women from Italy. Positive and significant linear correlation between Hg and Se was found in cord blood, maternal blood and breast milk of women in Slovenia, Croatia and Italy, while the association was poor and insignificant in women from Greece. Hg and Se were found to be associated also in blood of Slovenian women aged 50-59 and children aged 6-11 from mercury mine area, but not in children from other areas of Slovenia. Se in maternal and cord blood, but not in milk, was significantly correlated with the intake of many food items in pregnancy. The strongest direct associations regarded cheese and some vegetables (artichokes and fennels). In addition, both Hg and Se were significantly associated with fish consumption, possibly explaining correlations between these two elements found in selected biomarkers. Nevertheless, our observations might be also a consequence of a Se protective mechanism against mercury toxicity in certain populations.

Mercury inhibition towards the thioredoxin system and in particular to thioredoxin reductase (TrxR) is an important molecular mechanism of mercury toxicity. In the present work, the effects of mercuric chloride (HgCl₂) and monomethylmercury (MeHg) on TrxR were deeply investigated by relating activity and structure modification. Mass spectra analysis demonstrated the formation of adducts between mercury molecules and TrxR leading to inactivation and BIAM-labeling demonstrates the involvement of the active site selenocysteine in the inhibition. Selenite serves as an antagonist of mercury toxicity but molecular mechanism of detoxification is not clear. The effects of selenite on the inhibition of thioredoxin system by mercury were investigated. At concentrations higher than 5µM, TrxR displayed full activity recovery in selenite reduction assay and 70-80% activity recovery in thioredoxin-dependent insulin reduction assay. The structural analysis by MS indicated that a mercury was replaced from the selenenylsulfide adduct by selenium possibly with the formation of mercury(II) selenide. The detoxified TrxR could be identified through the formation of a diselenide bond (-Se-Se) with the active site 498 SeCys. These results stress the role of TrxR as a target of mercurials and provide the mechanism of selenium as a detoxicant agent of mercury poisoning.

Several large-scale human methylmercury poisonings have occurred and human exposure to lower-level methylmercury through consumption of methylmercury-containing fish and other seafood is widespread. Despite public health concerns little is known about the molecular mechanisms by which methylmercury causes its toxic effects and the role of selenium therein. Synchrotron X-ray absorption spectroscopy (XAS) can be used to investigate the chemical speciation of an element of interest in biological tissues in situ whereas synchrotron X-ray fluorescence imaging (XFI) can directly visualize the distribution of the element in the studied specimen. Here we used XAS and XFI to investigate the molecular nature of mercury and selenium in human brain tissue taken from five individuals with varying mercury exposure (two individuals with acute exposure to high levels of methylmercury, two individuals with a lifetime of high fish consumption, and one subject with minimal fish consumption and no known exposure) (Korbas et al. ACS Chem. Neurosci., 2010, 1, 810-818). After high exposures to methylmercury, the cortical brain selenium levels were significantly elevated and the mercury was present in at least two chemically distinct species, inert nano-particulate mercuric selenide and mobile mercuric bis-thiolate. In one case, substantial fraction of mobile methylmercury cysteineate species was also detected. After low chronic methylmercury exposures, the cortical selenium levels appeared normal and the predominant forms of mercury were mercuric selenide and methylmercury cysteineate, both at much lower levels. Interestingly, the levels of total organic selenium (presumably the selenium naturally present fulfilling functional roles in selenoenzymes) were not disturbed in all of the cases.

To study the origin of the selenium involved in forming mercuric selenide deposits we exposed zebrafish larvae to mercuric chloride or methylmercury cysteineate. Following inorganic mercury exposure, micro-deposits of mercuric selenide were detected in the brain and the kidney tubules using XFI. These were accompanied by very low levels of natural selenium in the melanophores (black pigment cells) when compared to control and methylmercury-treated larvae, thus identifying melanophores as the plausible source of mobile selenium pool.

Our results clearly demonstrate that selenium plays an essential role in the detoxification process of inorganic and organic mercury.

Owing to a long history of mercury-related activities, local residents in Wanshan, China, have suffered from elevated mercury exposure. The objective of the present study was to assess the effects of supplementation with selenium-enriched yeast in long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 were supplemented with 100 µg of organic selenium daily as selenium-enriched yeast for 3 months while the left 50 volunteers were supplemented with placebo. Quantitative analyses of mercury and selenium levels as well as the examination of the influence on oxidative stress-related biomarkers in urine samples on different days were conducted. Significantly increased urinary mercury excretion was observed. The urinary malondialdehyde concentrations and urinary 8-hydroxy-2’-deoxyguanosine concentration decreased significantly after selenium supplementation. This 3-month selenium supplementation trial indicates that daily supplementation of 100 µg of selenium in the form of selenium-enriched yeast can help the urinary excretion of mercury and decrease oxidative damage to lipids and DNA in those long-term mercury exposed people.