Browsing by Author "Thurbide, Kevin M."

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    Application of Metallomics Tools to Probe the Toxicological Chemistry of Cadmium and Mercury with Blood Plasma Constituents
    (2023-04-24) Gautam, Astha; Gailer, Jurgen; Musgrove, Amanda S.; Thurbide, Kevin M.
    The chronic low-level exposure of humans to toxic metal pollutants is associated with severe adverse health effects, but the involved biomolecular mechanisms in the bloodstream - which ultimately define the exposure-response relationships - are incompletely understood. The inorganic pollutants that I focused on include the nephrotoxin Hg2+ and the carcinogen Cd2+. Human serum albumin (HSA) - the most abundant plasma protein - has distinct binding sites for Hg2+ and Cd2+ and it is implicated in their delivery to target organs, but the role that L-cysteine (Cys) and D,L-homocysteine (hCys) play in this process is less well understood. To gain insight into the roles that these biomolecules play in this translocation from bloodstream to target organs I applied analytical tools. In the first step, we identified the toxicologically relevant Cd-Cys complexes that can be formed under physiological conditions of blood plasma. To this end, we employed an anion exchange HPLC column coupled to a flame atomic absorption spectrometer (FAAS) and we used a mobile phase that resembled protein free blood plasma. The observation of the retention behaviour of Cd2+ on this HPLC-FAAS system as a function of increasing Cys concentrations allowed us to observe the on-column formation of mixed CdCysxCly complexes, some of which were characterised by X-ray absorption spectroscopy. In the second step, we wanted to gain insight into the role that HSA plays in the translocation of Hg2+ and Cd2+ to organs. To this end, a size-exclusion chromatography (SEC) coupled on-line to an inductively coupled plasma atomic emission spectrometer (ICP-AES) was employed. The injection of an HSA-Hg/Cd complex with increasing mobile phase concentrations of Cys and hCys allowed us to observe the integrity of the HSA-Hg/Cd complex, which provided new insight into the translocation of Cd2+ and Hg2+ to toxicological target organs.