Hormesis and Cosmetic Dermatology

By: Haw-Yueh Thong, MD, MS, Department of Dermatology of National Taiwan University Hospital; and Howard I. Maibach, MD, University of California School of Medicine

Posted: February 26, 2009, from the March 2009 issue of Cosmetics & Toiletries.

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It is believed that this modest stimulatory responsiveness is the result of a compensatory process that slightly “overshoots” its goal of the original physiological set-point, ensuring that the system returns to homeostasis without unnecessary and excessive overcompensation.⁸ Therefore, it is important to follow the dose-response relationships over time to better define their quantitative features.

While initial interest has been focused on the hormetic effects of pollutants and toxic substances on biological systems,⁹ interest has expanded to include pharmacological agents and phyto-compounds, as well as endogenous agonists.⁷ Hormetic-like biphasic dose response relationships appear to be highly generalizable; that is, such responses do not appear to be restricted by biological model, endpoint or chemical/physical stressors.⁷

Several investigations have attempted to assess mechanisms that could account for the hormetic-like biphasic dose-response relationship. In general, there is no single mechanism that can account for the plethora of hormetic relationships. Nonetheless, a common molecular tactic by which biphasic dose-response relationships are displayed involves the presence of two receptor subtypes affecting cell regulation, one with high and the other with low affinity for the agonist but with notably more capacity (i.e., more receptors).⁷ Such an arrangement may lead to the biphasic dose response, with the high-affinity receptor activated at low concentrations, which stimulates DNA synthesis and cellular proliferation; and the low-affinity/high-capacity receptor becoming dominant at higher concentrations, decreasing the cell proliferative response. This is a general pharmacological mechanism in that it is employed for a large number of receptor-based responses, from cancer cells to neutrophil chemotaxis and many others.

Hormesis Considerations in Toxicology Assessments
Calabrese and Blain¹⁰ have compiled a hormesis database containing 5,600 hormetic-like dose response relationships and more than 900 agents from a broadly diversified spectrum of chemical classes and physical agents. This compilation stresses the robustness of the published body of work supporting the hormetic dose-response hypothesis. However, despite the extensive observation of hormetic dose-response relationships, most studies have assessed cellular responses and few have continued the work with animal and human models, normal or diseased, or have assessed the simultaneous responses of different systems to the same agent. In vivo studies are necessary to provide an integrative assessment of the whole animal/human response to various agents, to document any discrepancies between in vitro and in vivo responses, and to clarify the clinical implication of hormesis.

Another issue to consider regarding hormesis, as proposed by van Der Woude,¹¹ is the need to modify riskassessment paradigms to take hormesis into account. Further, Rietjens and Alink12 suggest that toxicology studies should examine not only the adverse effects at high levels of exposure, but also the complex biological effects, adverse and beneficial, at low levels of exposure. Low-dose toxicology and pharmacology will contribute to developing better methods of low-dose risk assessment of chemical compounds and their effect on carcinogenesis by considering that the ultimate biological effect of a chemical may vary with its dose, the endpoint or target organ considered, cellular interactions, and/or the combined exposure with other chemicals.