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Structural Characterization of Toxicologically Relevant Cd(2+)-L-Cysteine Complexes

The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd(2+) in the bloodstream, we employed an anion-exchange HPLC coupled...

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Detalles Bibliográficos
Autores principales: Gautam, Astha, Gomez, Amanda, Mendoza Rengifo, Emérita, George, Graham N., Pickering, Ingrid J., Gailer, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144473/
https://www.ncbi.nlm.nih.gov/pubmed/37112521
http://dx.doi.org/10.3390/toxics11040294
Descripción
Sumario:The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd(2+) in the bloodstream, we employed an anion-exchange HPLC coupled to a flame atomic absorption spectrometer (FAAS) using a mobile phase of 100 mM NaCl with 5 mM Tris-buffer (pH 7.4) to resemble protein-free blood plasma. The injection of Cd(2+) onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl(3)](−)/[CdCl(4)](2−) complexes. The addition of 0.1–10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd(2+), which was rationalized by the on-column formation of mixed CdCys(x)Cl(y) complexes. From a toxicological point of view, the results obtained with 0.1 and 0.2 mM Cys were the most relevant because they resembled plasma concentrations. The corresponding Cd-containing (~30 μM) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd(2+) when the Cys concentration was increased from 0.1 to 0.2 mM. The putative formation of these toxicologically relevant Cd species in blood plasma was implicated in the Cd uptake into target organs and underscores the notion that a better understanding of the metabolism of Cd in the bloodstream is critical to causally link human exposure with organ-based toxicological effects.