Physiologically relevant hCys concentrations mobilize MeHg from rabbit serum albumin to form MeHg-hCys complexes.

Methylmercury (MeHg) is one of the most potent neurotoxins to which humans are exposed via the consumption of fish, from which it is effectively absorbed via the gastrointestinal tract into the bloodstream. Its interactions with plasma proteins, small-molecular-weight (SMW) molecules, and red blood cells, however, are incompletely understood, but critical as they determine whether and how much MeHg reaches target organs. To better define the role that SMW thiols play in the delivery of MeHg to known transporters located at the placental and blood-brain barrier, we have employed size exclusion chromatography-inductively coupled plasma-atomic emission spectroscopy to analyze MeHg-spiked rabbit plasma in the absence and presence of SMW thiols dissolved in the phosphate-buffered saline buffer mobile phase. While 300 µM methionine did not affect the binding of MeHg to rabbit serum albumin (RSA), cysteine (Cys), homocysteine (hCys), and glutathione resulted in the elution of the main Hg peak in the SMW elution range. In addition, 50 µM of hCys or Cys in the mobile phase resulted in the mobilization of MeHg from RSA in rabbit plasma and from pure RSA in solution. The Hg peak that eluted in the SMW elution range (50 µM of hCys) was identified by electrospray ionization-mass spectrometry as an MeHg-hCys complex. Since l-type amino acid transporters are present at the blood-brain barrier (BBB), which facilitate the uptake of MeHg-Cys species into the brain, our results contribute to establish the bioinorganic mechanisms that deliver MeHg to the BBB, which is critical to predict organ-based adverse health effects.

Toxic Metal Species and 'Endogenous' Metalloproteins at the Blood-Organ Interface: Analytical and Bioinorganic Aspects.

Globally, human exposure to environmental pollutants causes an estimated 9 million deaths per year and it could also be implicated in the etiology of diseases that do not appear to have a genetic origin. Accordingly, there is a need to gain information about the biomolecular mechanisms that causally link exposure to inorganic environmental pollutants with distinct adverse health effects. Although the analysis of blood plasma and red blood cell (RBC) cytosol can provide important biochemical information about these mechanisms, the inherent complexity of these biological matrices can make this a difficult task. In this perspective, we will examine the use of metalloentities that are present in plasma and RBC cytosol as potential exposure biomarkers to assess human exposure to inorganic pollutants. Our primary objective is to explore the principal bioinorganic processes that contribute to increased or decreased metalloprotein concentrations in plasma and/or RBC cytosol. Furthermore, we will also identify metabolites which can form in the bloodstream and contain essential as well as toxic metals for use as exposure biomarkers. While the latter metal species represent useful biomarkers for short-term exposure, endogenous plasma metalloproteins represent indicators to assess the long-term exposure of an individual to inorganic pollutants. Based on these considerations, the quantification of metalloentities in blood plasma and/or RBC cytosol is identified as a feasible research avenue to better understand the adverse health effects that are associated with chronic exposure of various human populations to inorganic pollutants. Exposure to these pollutants will likely increase as a consequence of technological advances, including the fast-growing applications of metal-based engineering nanomaterials.