Molecular Fates of Organometallic Mercury in Human Brain

Abstract

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure, we observe the presence of biologically less available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.

Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases

“…Understanding whether the increased cumulative influx of these inorganic pollutants into the human bloodstream is tolerable or causally linked to more environmental diseases than we are currently aware of requires a mechanism-driven integrated approach which hinges on the elucidation of bioinorganic chemistry processes involving As III , Cd 2+ , Hg 2+ , CH 3 Hg + and Pb 2+ in the GI-tract–bloodstream–organ system. While the application of synchrotron radiation-based advanced spectroscopic tools have already provided structural information about the chemical nature of Hg and Cd in various human target organs [ 146 , 147 ], our fragmentary knowledge about their individual interactions with biomolecules in blood plasma, RBCs and within organs must be considerably advanced to further detail the mechanisms of the chronic toxicity for individual toxic metal(loids) species as these define—over time—whether the outcome for any given human will be health or disease. To this end, results from studies into the bioinorganic processes that unfold in the bloodstream (e.g., RBC rupture) need to be integrated with those that unfold in target organs (e.g., ferroptosis), as all toxic species that impinge on any given organ and are internalized ultimately determine the resulting organ damage [ 148 ].…”

More Effective Mobilization of Hg2+ from Human Serum Albumin Compared to Cd2+ by L-Cysteine at Near-Physiological Conditions

“…Secondly, the results that were obtained for Cd 2+ imply that up to four distinct Cd species ( Figure 2 , bottom, red arrows) will subsequently impinge on target organs and—based on their relative organ uptake—determine toxic adverse effects therein. Taken together, these findings provide deeper insight into the dynamic bioinorganic mechanisms that deliver specific Cd 2+ and Hg 2+ species to their corresponding toxicological target organs [ 59 ]. Given that both Hg 2+ and Cd 2+ are established nephrotoxins [ 43 , 60 ], it is interesting to point out that both metals formed Cys complexes that eluted at about the same retention time, implying a closely related structure ( Figure 2 ).…”

Atomic spectrometry update: review of advances in the analysis of clinical and biological materials, foods and beverages

“…Speciation analysis of Hg and Se in human brain tissue samples using HERFD-XAS was used to evaluate the differences between chronic low-level and short-term high level methyl mercury exposure from fish consumption . 173 Samples were collected from subjects representing chronic long-term low-level Hg exposure ( n = 4), short-term high-level exposure with long-term ( n = 1) and shorter-term ( n = 2) survival as well as healthy controls with no known exposure to Hg ( n = 2). Brain tissue from long-term low-level exposure showed MeHg coordinated to an aliphatic thiolate as previously seen in marine fish.…”