Boron enhances adaptive responses and biological performance via hormetic mechanisms

This article provides the first extensive documentation of mechanisms of hormetic dose/concentration responses. The mechanisms selected were principally those mediated via receptor and/or cell signaling pathways. Mechanisms are reported for greater than 100 agents affecting nearly 400 dose/concentration responses from a wide range of chemical classes, affecting a broad range of cell types and endpoints. Regardless of the model (i.e. in vitro or in vivo), inducing agent, endpoint, or receptor/cell signaling pathway mediated mechanism, the quantitative features of the hormetic dose/concentration responses are similar, suggesting that the magnitude of the response is a measure of biological plasticity, within a broad range of biological contexts. These findings represent an important advance in the understanding of the hormetic dose/concentration response, its generalizability and potential biomedical applications, including drug discovery/efficacy assessment and the risk assessment process.

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.