Markers of combined aerogenic exposure to metal oxides and transformed plasma proteomic profiles in children

Changes in homeostatic balance of the body, primarily at the cellular-molecular level, are a relevant research object in fundamental and applied studies. They can be eligible indicators for predicting negative effects under exposure to chemical risk factors. The aim of this study was to substantiate markers of a transformed plasma proteomic profile in children. These markers should have prognostic value and an evidence-based association with combined aerogenic exposure to metal oxides (copper and nickel oxides used as an example). We propose an innovative methodical approach based on plasma proteomic profiling that includes the following: identification of identical proteins and genes encoding their expression; quantification of indicators within the ‘identical protein - a chemical concentration in blood’ system; prediction of negative effects as per indicators of homeostasis destabilization at the cellular-molecular level under chronic aerogenic exposure to chemicals. The proposed algorithm was tested by comparing changed proteins and peptides identified in plasma proteomic profiles of children exposed simultaneously to nickel and copper oxides in ambient air in actual conditions and small rodents under experimental combined and isolated exposure to the analyzed chemicals in levels equal to real ones. Long-term aerogenic exposure simultaneously to copper and nickel oxides was established to create elevated nickel and copper levels in blood of exposed children substantiated as markers of exposure. They were up to 2.4 times higher against the same indicators in unexposed children and reference levels as well. The results of field observations were verified by elevated levels of the same chemicals in blood under experimental modeling of an equivalent combined exposure performed on biological models. APOBEC1 complement factor (the А1CF gene) was substantiated as an identical proteomic marker based on plasma proteomic profiling in experimental and field investigations. It has an evidence-based association with markers of exposure (nickel and copper simultaneously identified in blood). Lower expression of this protein under persistent combined aerogenic exposure to nickel and copper oxides makes it possible to predict such a negative effect as modification of low density lipoproteins with further induction of atherosclerotic changes in vessels, the latter being a risk factor of cardiovascular diseases.