Exposure-Response Relationship of Toxic Metal(loid)s in Mammals: Their Bioinorganic Chemistry in Blood Is an Intrinsic Component of the Selectivity Filters That Mediate Organ Availability

哺乳动物体内有毒金属(类金属)的暴露-反应关系:其在血液中的生物无机化学性质是介导器官利用率的选择性过滤器的固有组成部分

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Abstract

The gastrointestinal tract mediates the absorption of nutrients from the diet, which is increasingly contaminated with toxic metal(loid) species (TMs) and thus threatens food safety. Evidence in support of the influx of TMs into the bloodstream of the general and vulnerable populations (babies, children, pregnant women, and industrial workers) has been obtained by accurately quantifying their blood concentrations. The interpretation of these TM blood concentrations, however, is problematic, as we cannot distinguish between those that are tolerable from those that may cause the onset of environmental diseases. Since TMs that have invaded the bloodstream may perturb biochemical processes therein that will eventually cause organ damage it is crucial to better understand their bioinorganic chemistry as these processes collectively determine their organ availability. Thus, bioinorganic processes of TMs in the bloodstream represent selectivity filters which protect organs from their influx and ultimately determine the corresponding exposure-response relationships. The need to better understand selectivity filters prompted us to mechanistically disentangle them into the major bioinorganic chemistry processes. It is argued that the detoxification of TMs in the bloodstream and the biomolecular mechanisms, which mediate their uptake into target organs, represent critical knowledge gaps to revise regulatory frameworks to reduce the disease burden.

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