A computational study toward the "personalized" activity of alternariol - Does it matter for safe food at individual level?

Abstract

Mycotoxins in food may threat public health at a global scale. However, for most of them, the current body of knowledge does not support a proper risk assessment and more data are needed to clarify their toxicity. In particular, the assessment of "personalized" action may succeed in understanding and counteracting the effects of many toxicants. Therefore, the assessment of "personalized" toxicology of mycotoxins might deserve attention to foster the understanding of their mechanisms of toxicity and to eventually improve the assessment of risk. This work dealt with the early warning analysis of possible differences in eliciting androgenic stimuli by alternariol, a widespread mycotoxin produce by Alternaria species, when mutations on the androgen receptor occur. It was applied a computational study based on docking simulations, pharmacophore modeling and molecular dynamics to assess the capability of alternariol to interact with the androgen receptor bearing the M749I substitution - which confers insensitivity to androgens stimulation. The results collected pointed to possible "protective" effects against alternariol suggesting: i) the likely existence of inter-individual responses to alternariol stimulation; ii) the meaningfulness of collecting data on "personalized" response to mycotoxins toward a more precise paradigm addressing the risk assessment at the individual level.

Keywords: Alternariol; Androgen receptor; Androgenic activity; Personalized toxicology; Toxicodynamic.