Organ damage by toxic metals is critically determined by the bloodstream

Abstract

Past poisoning epidemics have revealed that the chronic exposure to exceedingly small daily doses of toxic metal and metalloid species can – over time – severely affect human health. Today, several potentially toxic metals and metalloids have been accurately quantified in the bloodstream of the average population, but the interpretation of these from a public health point of view remains problematic. Conversely, the biomolecular origin for a multitude of grievous human diseases remains unknown. Supported by recent epidemiological evidence, these seemingly unrelated facts suggest that human exposure to the aforementioned pollutants may be linked to the etiology of more adverse health effects than we currently know. Based on the interaction of toxic metal and metalloid species with essential trace elements, plasma and erythrocytes in the bloodstream, we have previously argued that a better understanding of these bioinorganic chemistry processes are destined to provide important new insight into their mechanisms of chronic toxicity. This perspective provides an update on recent advances to better understand these bioinorganic processes and attempts to integrate these findings with the whole organism in order to establish connections with the etiology of human diseases. Based on the recent observation of the arsenite-induced perturbation of the whole-body distribution of selenite in mammals and the mercuration of hemoglobin in erythrocyte cytosol it is argued that bioinorganic processes in the bloodstream critically determine which metal and/or non-metal containing species will impinge on the toxicological target organ(s). Accordingly, the bioinorganic chemistry that unfolds in the bloodstream represents a critical bottleneck in terms of linking the exposure of humans to toxic metal species with the etiology of diseases. Furthermore, a better understanding of the blood-based detoxification of environmentally abundant toxic metal species is of direct practical use to develop palliative treatments to ameliorate the adverse effect that toxic metal species exert on certain human populations.