Cadmium toxicity in Mus musculus mice based on metallomic and metabolomic approaches. Antagonistic interaction between Se and Cd in the bloodstream

Abstract

Cadmium (Cd) is an important inorganic toxicant in the environment which impacts on human health. A metallomic approach based on size-exclusion chromatography (SEC) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and multidimensional chromatography separation based on SEC coupled to affinity chromatography 2D-SEC-AF-ICP-MS have been applied to achieve a better understanding of the function, detoxification processes and regulation of metals in mice (Mus musculus) under controlled exposure to both Cd and Cd plus 77Se. Isotopic dilution analysis (IDA) was performed to quantify selenium containing proteins in mice plasma with ICP-qMS as a multielemental detector. Additionally, isotope pattern deconvolution (IPD) was applied to study the fate of enriched 77selenite in mice subjected to cadmium exposure and the effect of selenoprotein production in plasma. Moreover, the affinity of Cd for SeP in plasma of mice was corroborated using anion exchange chromatography (AEC) after AF separation and identified by organic mass spectrometry. This work illustrates the high reliability of the integrated use of inorganic and organic mass spectrometry to get a metallomic approximation, which provides a good alternative to gain deep insight into the fate of elements in exposed organisms, providing information about metal trafficking, interactions and homeostasis.