Application of Metallomics Tools to Probe the Toxicological Chemistry of Cadmium and Mercury with Blood Plasma Constituents
Date
2023-04-24
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Abstract
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.
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Keywords
Toxic Metals, Mercury, Cadimum, Thiols
Citation
Gautam, A. (2023). Application of metallomics tools to probe the toxicological chemistry of cadmium and mercury with blood plasma constituents (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.