Structural Characterization of Toxicologically Relevant Cd2+-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 Cd2+ 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 Cd2+ onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl3](-)/[CdCl4](2-) complexes. The addition of 0.1-10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd2+, 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 (similar to 30 mu M) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd2+ 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.

Automated summary

The exposure of humans to low chronic doses of Cd can have adverse health effects, but the biomolecular mechanisms behind this are not fully understood. In this study, an HPLC-FAAS system was used to investigate the chemistry of Cd2+ in the bloodstream. The addition of L-cysteine to the mobile phase affected the retention behavior of Cd2+, and the formation of CdCys(x)Cl(y) complexes on the column was observed. The formation of these toxicologically relevant Cd species in blood plasma may be implicated in the uptake of Cd into target organs and the resulting toxicological effects.