Ligand-Mediated Toxicology: Characterization and Translational Prospects

In biochemistry a ligand is a molecule that binds to a receptor or other biomolecule that forms a complex and produces a biological effect. We live in a world of exposure to exogenous ligands and there are three long-established strands of biological research that have investigated the actions of biologically active dietary or environmental compounds on animals, including humans. First, in agricultural and animal husbandry research, there is extensive documentation of the many thousands of phytochemicals that mediate plant-animal interactions many of which produce toxic effects at certain levels of exposure in terms of dose, duration and window of sensitivity. In a broader biological context, many of these relationships have been formalized by concepts of co-evolution of plants and animals. Second, there is a long history of toxicology research showing a wide range of adverse effects that often result from exposures to hormones and other modulators of endocrine function, especially during developmentally sensitive intervals. In recent decades much of this research has been encapsulated by a single term of “endocrine disruptors” even though many ligand-mediated actions are not endocrine per se or definitively adverse. Third, nutritional and functional foods research have demonstrated a wide range of health benefits produced by consumption of many phytochemical ligands through mechanisms that are not truly distinct from those that seem to mediate the adverse effects noted in either the animal husbandry or developmental toxicology research arenas. We are confident that environmental and public health can be enhanced by defining how such exposures to exogenous signaling molecules (ligands) pose both risks and benefits. Therefore, it is time to modify the scientific perspective and nomenclature to encompass these several streams of investigation such that both risks and benefits of exposure to dietary and environmental ligands may be characterized and translated into sound strategies to address environmental and public health concerns. Fetal alcohol spectrum disorder (FASD) is an illustrative case for translational toxicology-informed interventions where there is a viable prospect for a multi-component nutritional health benefit to reduce occurrence or severity of FASD. Health promoting interventional options must include reduction(s) in exposures to ligands that incur health risks but when exposures cannot be adequately reduced or preempted, we should also define and employ active mechanistically-based mitigative interventions.https://nsuworks.nova.edu/hpd_corx_facbooks/1003/thumbnail.jp