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Hormesis in toxicology

Hormesis is a characteristic of many biological processes, namely a biphasic or triphasic response to exposure to increasing amounts of a substance or condition. Within the hormetic zone, the biological response to low exposures to toxins and other stressors is generally favorable. The term “hormesis” comes from Greek hórmēsis “rapid motion, eagerness”, itself from ancient Greek hormáein “to set in motion, impel, urge on”, the same Greek root as the word hormone. The term ‘hormetics’ has been proposed for the study and science of hormesis.

In toxicology, hormesis is a dose response phenomenon to xenobiotics or other stressors characterized by a low-dose stimulation, with zero dose and high-dose inhibition, thus resulting in a J-shaped or an inverted U-shaped dose response (e.g. the arms of the “U” are inhibitory or toxic concentrations whereas the curve region stimulates a beneficial response.) Generally speaking, hormesis pertains to the study of benefits of exposure to toxins such as radiation or mercury (perhaps analogous to health paradoxes such as the smoker’s paradox, although differing by virtue of dose-dependent effects). Microdosing, and to some extent homeopathy, are often regarded as applications of hormesis.

In physiology and nutrition, hormesis can be visualized as a hormetic curve with regions of deficiency, homeostasis, and toxicity. Physiological concentrations deviating above or below homeostasis concentrations adversely affects an organism, thus in this context, the hormetic zone is synonymously known as the region of homeostasis. In pharmacology the hormetic zone is similar to the therapeutic window. Some psychological or environmental factors that would seem to produce positive responses have also been termed “eustress”.

In the context of toxicology, the hormesis model of dose response is vigorously debated.The biochemical mechanisms by which hormesis works (particularly in applied cases pertaining to behavior and toxins) remain under early laboratory research and are not well understood. The notion that hormesis is an important policy factor for chemical risk regulations is not widely accepted.

Further References

Calabrese, E. J., & Baldwin, L. A.. (2002). Defining hormesis. Human and Experimental Toxicology

Plain numerical DOI: 10.1191/0960327102ht217oa
DOI URL
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Mattson, M. P.. (2008). Hormesis defined. Ageing Research Reviews

Plain numerical DOI: 10.1016/j.arr.2007.08.007
DOI URL
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Ullman, D.. (2021). Exploring Possible Mechanisms of Hormesis and Homeopathy in the Light of Nanopharmacology and Ultra-High Dilutions. Dose-Response

Plain numerical DOI: 10.1177/15593258211022983
DOI URL
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Calabrese, E. J.. (2014). Hormesis: A fundamental concept in biology. Microbial Cell

Plain numerical DOI: 10.15698/mic2014.05.145
DOI URL
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Calabrese, E. J.. (2020). Hormesis and ginseng: Ginseng mixtures and individual constituents commonly display hormesis dose responses, especially for neuroprotective effects. Molecules

Plain numerical DOI: 10.3390/molecules25112719
DOI URL
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Mcclure, C. D., Zhong, W., Hunt, V. L., Chapman, F. M., Hill, F. V., & Priest, N. K.. (2014). Hormesis results in trade-offs with immunity. Evolution

Plain numerical DOI: 10.1111/evo.12453
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Zimmermann, A., Bauer, M. A., Kroemer, G., Madeo, F., & Carmona-Gutierrez, D.. (2014). When less is more: Hormesis against stress and disease. Microbial Cell

Plain numerical DOI: 10.15698/mic2014.05.148
DOI URL
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Calabrese, E. J., & Mattson, M. P.. (2017). How does hormesis impact biology, toxicology, and medicine?. Npj Aging and Mechanisms of Disease

Plain numerical DOI: 10.1038/s41514-017-0013-z
DOI URL
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Calabrese, E. J.. (2018). Hormesis: Path and progression to significance. International Journal of Molecular Sciences

Plain numerical DOI: 10.3390/ijms19102871
DOI URL
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