Hormesis mechanisms

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

Mehendale HM. 1992. Biochemical mechanisms of biphasic dose-response relationships Role of hormesis. In Calabrese EJ, ed. Biological effects of low level exposures to chemicals and radiation. Workshop, Amherst, MA, April 30 - May 1, 1991. Chelsea, Ml Lewis Publishers, Inc., 59-94. 

Arumugam TV, Gleichmann M, Tang SC, Mattson MP. 2006. Hormesis/precondition-ing mechanisms, the nervous system and aging. Ageing Res Rev 5 165-178. 

A theory that has been gaining acceptance recently is that many chemicals have beneficial effects at very low doses and may perhaps stimulate protective mechanisms, and that as the dose increases the effects become adverse. This is known as hormesis and may occur as a result of more than one exposure to a chemical (see box). ... 

Induction of hormesis and adaptive responses by low dose radiation have been extensively studied (Wang et al, 2008). Pre-exposure of diabetic prone mice to low dose radiation (LDR) has reduced the incidence of alloxan diabetes and delayed the onset of hyperglycemia, although the mechanisms are unclear (Wang et al, 2008). Low intensity laser (LIL) has stimulated healing in diabetes (Wang et al., 2008). 

Eukushima, S., Kinoshita, A., Ruatanachokchai, R., Kushida, M., Wanibuchi, H., and Morimura, K. (2005a). Hormesis and dose-response-mediated mechanisms in carcinogenesis Evidence for a threshold in carcinogenicity of non-genotoxic carcinogens. Carcinogenesis 26, 1835-1845. 

Hormesis is not unique to EMs. It has been reported for several plant and animal species exposed to heavy metals, pesticides, polycyclic aromatic hydrocarbons, and other organic chemicals [67-69], Stebbing [68] suggested that hormesis is the cumulative consequence of transient and sustained overcorrections of biosynthesis, that is, a rate-controlled process controlled by the end-product inhibition. To date, however, no studies have identified the mechanisms responsible for hormetic effects of explosives at specific concentrations. 

The second hypothesis states that there is a threshold below which no harm accrues, and, further, that lower doses may even be beneficial. When a toxin at high levels is beneficial at low levels, it is called hormesis. Substances exhibiting hormesis are, for example, vitamin D, selenium, aspirin, table salt, water, and, for plants, fertilizer. There may even be a hormesis effect for low-level radiation because this might provide the stimulus for the heighteued activity of DNA repair mechanisms (Karam, 2003). 

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