Journal articles on the topic 'Hormesis'
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1
Rattan, Suresh IS, and Taru Deva. "Testing the hormetic nature of homeopathic interventions through stress response pathways." Human & Experimental Toxicology 29, no. 7 (June 17, 2010): 551–54. http://dx.doi.org/10.1177/0960327110369858.
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The scientific foundations of hormesis are now well established and include various biochemical and molecular criteria for testing the hormetic nature of chemicals and other modulators. In order to claim homeopathy as being hormetic, it is essential that, in addition to the hormetic biphasic dose response, homeopathic remedies should fulfill one or more molecular criteria. Since stress response pathways, such as heat shock response, antioxidative response, autophagic response and unfolded protein response, are integral components of the physiological hormesis, it is important that homeopathic drugs be tested for these pathways if these are to be considered as hormetins and to cause hormesis.
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Kitchin, Kirk T., and J. Wanzer Drane. "A critique of the use of hormesis in risk assessment." Human & Experimental Toxicology 24, no. 5 (May 2005): 249–53. http://dx.doi.org/10.1191/0960327105ht520oa.
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There are severe problems and limitations with the use of hormesis as the principal dose-response default assumption in risk assessment. These problems and limitations include: (a) unknown prevalence of hormetic doseresponse curves; (b) random chance occurrence of hormesis and the shortage of data on the repeatability of hormesis; (c) unknown degree of generalizability of hormesis; (d) there are dose-response curves that are not hormetic, therefore hormesis cannot be universally generalized; (e) problems of post hoc rather than a priori hypothesis testing; (f) a possible large problem of ‘false positive’ hormetic data sets which have not been extensively replicated; (g) the ‘mechanism of hormesis’ is not understood at a rigorous scientific level; (h) in some cases hormesis may merely be the overall sum of many different mechanisms and many different dose-response curves - some beneficial and some toxic. For all of these reasons, hormesis should not now be used as the principal dose-response default assumption in risk assessment. At this point, it appears that hormesis is a long way away from common scientific acceptance and wide utility in biomedicine and use as the principal default assumption in a risk assessment process charged with ensuring public health protection.
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Borak, Jonathan, and Greg Sirianni. "Hormesis: Implications for Cancer Risk Assessment." Dose-Response 3, no. 3 (May 1, 2005): dose—response.0. http://dx.doi.org/10.2203/dose-response.003.03.011.
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Current guidelines for cancer risk assessment emphasize a toxicant's “mode of action”, rather than its empirically derived dose-response relationship, for determining whether linear low-dose extrapolation is appropriate. Thus, for reasons of policy, demonstration of hormesis is generally insufficient to justify a non-linear approach, although it may provide important insights into the actions of toxicants. We evaluated dose-response characteristics of four carcinogens reported to have hormetic dose-response curves: cadmium chloride; ionizing radiation; PAHs; and, 2,3,7,8-TCDD. For each, the study that documented hormesis in one organ also provided evidence of non-hormetic dose-responses in other organs or non-hormetic responses for seemingly similar carcinogens in the same species and organs. Such inconsistency suggests toxicologic reasons that the finding of hormesis alone is not sufficient to justify use of non-linear low-dose extrapolations. Moreover, available data in those examples are not sufficient to know whether hormesis is a property of the toxicants, the target organ, or the exposed species. From the perspectives of cancer risk assessment, the greatest informational value of hormesis may be that it provokes mechanistic studies intended to explain why hormesis occurs.
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Greenwood, Sharon N., Regina G. Belz, and Brian P. Weiser. "A Conserved Mechanism for Hormesis in Molecular Systems." Dose-Response 20, no. 3 (July 2022): 155932582211093. http://dx.doi.org/10.1177/15593258221109335.
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Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this case, hormesis can be observed if simultaneous binding of substrate and competitor enhances a response of the homo-multimer. We characterized this mechanism of hormesis in binding experiments that analyzed the interaction of homotrimeric proliferating cell nuclear antigen (PCNA) with uracil DNA glycosylase (UNG2) and a fluorescein-labeled peptide. Additionally, the basic features of this molecular mechanism appear to be conserved with at least two enzymes that are stimulated by low doses of inhibitor: dimeric BRAF and octameric glutamine synthetase 2 (GS2). Identifying such molecular mechanisms of hormesis may help explain specific hormetic responses of cells and organisms treated with exogenous compounds.
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Calabrese, Edward J., and Linda A. Baldwin. "The Dose Determines the Stimulation (and Poison): Development of A Chemical Hormesis Database." International Journal of Toxicology 16, no. 6 (November 1997): 545–59. http://dx.doi.org/10.1080/109158197226874.
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A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer searches utilizing various keyword descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biologic endpoints were assessed, with growth responses the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude with the average low-dose maximum stimulation approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude with the upper end of the hormetic curve approaching the estimated no-observed-effect level (NOEL) for the particular endpoint. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of ≥ doses with <3 doses in the hormetic zone. The present analysis suggests that chem ical hormesis is a reproducible and generalizable biologic phenomenon. Over the last decade advances have been made providing mechanistic insight helpful in explaining the phenomenon of chemical hormesis in multiple biologic systems with various endpoints. The reason for the uncertainty surrounding the existence of hormesis as a “real phenomenon” is believed to be the result of its relatively infrequent observation in the literature due to experimental design considerations, especially with respect to the number of doses, range of doses, and endpoint selection.
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Calabrese, E. J., and L. A. Baldwin. "Radiation hormesis: the demise of a legitimate hypothesis." Human & Experimental Toxicology 19, no. 1 (January 2000): 76–84. http://dx.doi.org/10.1191/096032700678815611.
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This paper examines the underlying factors that contributed to the marginalization of radiation hormesis in the early and middle decades of the 20th century. The most critical factor affecting the demise of radiation hormesis was a lack of agreement over how to define the concept of hormesis and quantitatively describe its dose-response features. If radiation hormesis had been defined as a modest overcompensation to a disruption in homeostasis as would have been consistent with the prevailing notion in the area of chemical hormesis, this would have provided the theoretical and practical means to blunt subsequent legitimate criticism of this hypothesis. A second critical factor undermining the radiation hormesis hypothesis was the generally total lack of recognition by radiation scientists of the concept of chemical hormesis which was markedly more advanced, substantiated and generalized than in the radiation domain. The third factor was that major scientific criticism of low dose stimulatory responses was galvanized at the time that the National Research Council (NRC) was organizing a national research agenda on radiation and the hormetic hypothesis was generally excluded from the future planned research opportunities. Furthermore, the criticisms of the leading scientists of the 1930s which undermined the concept of radiation hormesis were limited in scope and highly flawed and then perpetuated over the decades by other ‘prestigious’ experts who appeared to simply accept the earlier reports. This setting was then linked to a growing fear of radiation as a cause of birth defects, mutation and cancer, factors all reinforced by later concerns over the atomic bomb. Strongly supportive findings on hormetic effects in the 1940s by Soviet scientists were either generally not available to US scientists or disregarded as part of the Cold War mindset without adequate analysis. Finally, a massive, but poorly designed, US Department of Agriculture experiment in the late 1940s to assess the capacity for low dose plant stimulation by radionuclides failed to support the hormetic hypothesis thereby markedly lessening enthusiasm for research and funding in this area. Thus, the combination of a failed understanding of the hormetic hypothesis and its linkage with a strong chemical hormesis database, flawed analyses by prestigious scientists at the critical stage of scientific research development, reinforced by a Cold War mentality led to marginalization of an hypothesis (i.e., radiation hormesis) that had substantial scientific foundations and generalizability.
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Agathokleous, Evgenios, Costas Saitanis, and Athina Markouizou. "Hormesis Shifts the No-Observed-Adverse-Effect Level (NOAEL)." Dose-Response 19, no. 1 (January 1, 2021): 155932582110016. http://dx.doi.org/10.1177/15593258211001667.
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Data from recent dose-response toxicological studies suggest that the no-observed-adverse-effect-level (NOAEL) may depend upon whether hormesis is present. A further examination of these data supports this hypothesis by showing that the NOAEL was greater for living units (organisms or cells) showing hormesis than for living units showing no hormesis. For example, some cancer tissue cells may exhibit hormetic responses to an anticancer drug while some other cancer tissue cells may not. These findings suggest that living units showing hormesis may also be less susceptible than living units not showing hormesis. However, these findings are preliminary and cannot be generalized or assumed to be a norm yet. New studies are needed to evaluate how NOAEL shifts depending on the occurrence of hormesis.
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Pickrell, John A., and Frederick W. Oehme. "Examining the risks and benefits of replacing traditional dose-response with hormesis." Human & Experimental Toxicology 24, no. 5 (May 2005): 259–64. http://dx.doi.org/10.1191/0960327105ht521oa.
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In responding to Drs Calabrese and Baldwin's question, ‘At what point, if ever, should hormesis be employed as the principal dose response default assumption in risk assessment?’, we examined the benefits of replacing traditional dose-response with hormesis. In general, hormesis provides more complete useful information for risk assessment than does traditional dose-response. A major limitation of using hormesis as a default assumption in risk estimation is the difficulty of differentiating complex low-level hormetic responses from the placebo effect. A second limitation is that hormesis merely further defines one response. Most toxicoses have many responses. The most complete information takes all responses and their connections into account.
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Calabrese, E. J., and L. A. Baldwin. "The marginalization of hormesis." Human & Experimental Toxicology 19, no. 1 (January 2000): 32–40. http://dx.doi.org/10.1191/096032700678815594.
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Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades ofthe 20th century. These factors include: (a) the close-association of hormesis with homeopathy lead to the hostility of modern medicine toward homeopathy thereby creating a guilt by association framework, and the carry-over influence of that hostility in the judgements of medically-based pharmacologists/ toxicologists toward hormesis; (b) the emphasis of high dose effects linked with a lack of appreciation of the significance of the implications of low dose stimulatory effects; (c) the lack of an evolutionary-based mechanism(s) to account for hormetic effects; and (d) the lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.
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Calabrese, Edward J., Gaurav Dhawan, Rachna Kapoor, Ivo Iavicoli, and Vittorio Calabrese. "HORMESIS: A Fundamental Concept with Widespread Biological and Biomedical Applications." Gerontology 62, no. 5 (November 5, 2015): 530–35. http://dx.doi.org/10.1159/000441520.
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Hormesis is a biphasic dose response with specific quantitative features for the amplitude and width of the stimulation. It is highly generalizable and independent of biological model, endpoint, inducing agent, level of biological organization and mechanism. Hormesis may be induced via a direct stimulation or by overcompensation to a disruption of homeostasis. The induction of hormesis by low-level stressor agents not only rapidly upregulates adaptive processes to repair damage but also protects the adapted system from damage due to a subsequent challenging dose (toxic) within a definable temporal window. The striking consistency of the amplitude of hormetic response suggests that hormesis provides a quantitative description of biological plasticity. Knowledge of hormesis has particular potential biomedical significance with respect to slowing or retarding both normal aging processes and the progression of severe neurological diseases.
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Jonas, Wayne B., and John A. Ives. "Should we explore the clinical utility of hormesis?" Human & Experimental Toxicology 27, no. 2 (February 2008): 123–27. http://dx.doi.org/10.1177/0960327108090754.
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The idea that low-dose adaptive effects as described in hormesis can be used clinically has been discussed for hundreds if not thousands of years. Paracelsus famous adage that `the dose makes the poison' and the common folk saying that one can be cured by `the hair of the dog that bit you' speak to this idea. So why has so little research been done on the possible clinical utility of hormesis? What areas of clinical hormesis seem to be the most promising to explore? This article examines these concepts and proposes some initial areas or research where the possible utility of hormeiss might be investigated.
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Carelli, G., and I. Iavicoli. "Defining hormesis: the necessary tool to clarify experimentally the low dose–response relationship." Human & Experimental Toxicology 21, no. 2 (February 2002): 103–4. http://dx.doi.org/10.1191/0960327102ht219oa.
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The authors comment on Calabrese and Baldwin's paper ‘Defining Hormesis’, which, to date, is the first attempt to provide a definition of hormesis that goes beyond the different interpretations of this phenomenon reported in the literature. While appreciating the effort made in this study to place hormesis in a general and at the same time specific context, the authors believe some clarifications are needed as regards the quantitative features of this phenomenon. In this connection, they speculate on whether Calabrese and Baldwin think it appropriate to include hormesis assessment criteria in the document, referring in particular to those reported in a previous paper. The authors share Calabrese and Baldwin's conclusion that future experimental models designed to study hormetic phenomena must necessarily include the time factor, which not only guarantees this phenomenon will be detected, but is also able to detect the specific type of hormesis.
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Wiener, Jonathan B. "Hormesis, hotspots and emissions trading." Human & Experimental Toxicology 23, no. 6 (June 2004): 289–301. http://dx.doi.org/10.1191/0960327104ht451oa.
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Instrument choice - the comparison of technology standards, performance standards, taxes and tradable permits - has been a major topic in environmental law and environmental economics. Most analyses assume that emissions and health effects are positively and linearly related. If they are not, this complicates the instrument choice analysis. This article analyses the effects of a nonlinear dose-response function on instrument choice. In particular, it examines the effects of hormesis (highdose harm but low-dose benefit) on the choice between fixed performance standards and tradable emissions permits. First, the article distinguishes the effects of hormesis from the effects of local emissions. Hormesis is an attribute of the dose-response or exposure-response relationship. Hotspots are an attribute of the emissions-exposure relationship. Some pollutants may be hormetic and cause local emissions-exposure effects; others may be hormetic without causing local emissionsexposure effects. It is only the local exposure effects of emissions that pose a problem for emissions trading. Secondly, the article shows that the conditions under which emissions trading would perform less well or even perversely under hormesis, depend on how stringent a level of protection is set. Only when the regulatory standard is set at the nadir of the hormetic curve would emissions trading be seriously perverse (assuming other restrictive conditions as well), and such a standard is unlikely. Moreover, the benefits of the overall programme may justify the risk of small perverse effects around this nadir. Thirdly, the article argues that hotspots can be of concern for two distinct reasons, harmfulness and fairness. Lastly, the paper argues that the solution to these problems may not be to abandon market-based incentive instruments and their cost-effectiveness gains, but to improve them further by moving from emissions trading and emissions taxes to risk trading and risk taxes. In short, the article argues that hormesis does not pose a general obstacle to emissions trading or emissions taxes, but that in those cases where hormesis does pose such a problem, a shift toward risk trading or risk taxes would be the superior route.
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Oberbaum, Menachem, Shepherd Roee Singer, and Noah Samuels. "Hormesis and homeopathy: Bridge over troubled waters." Human & Experimental Toxicology 29, no. 7 (June 17, 2010): 567–71. http://dx.doi.org/10.1177/0960327110369777.
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Homeopathy is an empirical method of treatment. Hormesis, while stemming from within the rationalist tradition, has yet to be explained according to current pharmacological theory. Both share in common sub-threshold doses of toxic substances and an initial semi-toxicological insult followed by a greater compensatory (or healing) response. We question whether the differences between these fields may be amenable to scientific research. We identify five cardinal differences between homeopathy and hormesis: (1) Hormesis is a universal phenomenon, while homeopathy is highly specific; (2) Hormesis uses only measurable quantities of compounds, as opposed to homeopathy, which frequently administers medicines at dilutions far beyond the material range; (3) Preparation of hormetic solutions follows standard laboratory procedure, while homeopathy requires a sequential series of dilutions, each followed by vigorous shaking (‘succussion’); (4) The effects of hormesis are moderate and temporary, while homeopathy claims curative and permanent responses and (5) Hormesis is a lab phenomenon observed primarily in healthy organisms, whereas homeopathy is a mode of treatment administered primarily to ailing individuals. We believe that all five of these differences are amenable to scientific investigation, and suggest comparing succussed to non-succussed diluted solutions as an optimal first evaluation. We conclude that while certain differences exist between hormesis and homeopathy, hormesis may in fact be a subset of homeopathy.
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Kim, Steven B., Scott M. Bartell, and Daniel L. Gillen. "Inference for the existence of hormetic dose–response relationships in toxicology studies." Biostatistics 17, no. 3 (February 12, 2016): 523–36. http://dx.doi.org/10.1093/biostatistics/kxw004.
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Abstract In toxicology studies hormesis refers to a dose–response relationship with a stimulatory response at low doses and an inhibitory response at high doses. In this manuscript, we particularly focus on a J-shaped dose–response relationship for binary cancer responses. We propose and examine two new flexible models for testing the hypothesis of hormesis in a Bayesian framework. The first model is parametric and enhances the flexibility of modeling a hormetic zone by using a non-linear predictor in a multistage model. The second model is non-parametric and allows multiple model specifications, weighting the contribution of each model via Bayesian model averaging (BMA). Simulation studies show that the non-parametric modeling approach with BMA provides robust sensitivity and specificity for detecting hormesis relative to the parametric approach, regardless of the shape of a hormetic zone.
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Vasylkovska, Ruslana, Natalia Petriv, and Halyna Semchyshyn. "Carbon Sources for Yeast Growth as a Precondition of Hydrogen Peroxide Induced Hormetic Phenotype." International Journal of Microbiology 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/697813.
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Hormesis is a phenomenon of particular interest in biology, medicine, pharmacology, and toxicology. In this study, we investigated the relationship between H2O2-induced hormetic response inS. cerevisiaeand carbon sources in yeast growth medium. In general, our data indicate that (i) hydrogen peroxide induces hormesis in a concentration-dependent manner; (ii) the effect of hydrogen peroxide on yeast reproductive ability depends on the type of carbon substrate in growth medium; and (iii) metabolic and growth rates as well as catalase activity play an important role in H2O2-induced hormetic response in yeast.
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Bailer, A. J. "Experiments, analyses and decisions: hormesis in ecotoxicology." Human & Experimental Toxicology 20, no. 10 (October 2001): 507–9. http://dx.doi.org/10.1191/096032701718120346.
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We have been challenged by Peter Chapman to consider the implication of hormesis for both ecotoxicology and ecological risk assessment. A consideration of his proposal led to the following observations and comments. I echo his comments related to the need for experimental designs and statistical tools that accommodate and address hormesis. I expand on his comments related to the basic question of how adverse responses should be defined for hormetic concentration–response patterns for both individual species and populations. Finally, I reflect on the notion of the implication of incorrectly detecting or not detecting hormesis in an ecosystem.
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Meiliana, Anna, and Andi Wijaya. "Hormesis in Health and Disease: Molecular Mechanisms." Indonesian Biomedical Journal 12, no. 4 (December 2, 2020): 288–303. http://dx.doi.org/10.18585/inabj.v12i4.1315.
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BACKGROUND: Hormesis was initially defined as a phenomenon where a small dose of harmful agent exposure to living organisms gives beneficial effects. The dose and time of this ‘tress’ exposure has become the object of investigation across the broad range of biomedical studies.CONTENT: Hormesis characterized by the biphasic dose-effect or time-effect relationship for any substance. Some hormetic mechanisms performed biological plasticity, involve oxidative damage which instead induce antioxidant enzyme production in various cells. Early-life stress can increase resilience in later life and lack of stress can lead to vulnerability. Many stressors like dietary factors and natural environmental toxins can be occupied for healthy growth or homeostasis, which exemplifies how illness is the doorway to health.SUMMARY: Hormesis reconcile many paradoxical phenomena exert opposite effects of the same substance, either a xenobiotic or an endogenous substance, a hormone or a metabolite, a genetic manipulation or an epigenetic alteration, an experimental intervention or a natural event. Human bodies are highly adaptive. A resilient body would be resulted after the ‘training’. In this review, we will elucidate the hormesis’ definition, mechanisms and pathways, and also how hormesis impacts in human health and lifespan.KEYWORDS: biphasic, cell signaling, dose response, hormesis, preconditioning
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Bailer, A. John, and James T. Oris. "Incorporating hormesis in the routine testing of hazards." Human & Experimental Toxicology 17, no. 5 (May 1998): 247–50. http://dx.doi.org/10.1177/096032719801700505.
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The phenomenon of subtoxic stimulation of organism response is not uncommon in aquatic toxicology experiments. We describe the presence of hormesis in both growth and reproduction experiments in aquatic toxicology where these responses are observed in both animals and plants and at different trophic levels of an ecosystem. The implications of ignoring hormetic responses in the analysis of toxicity data are discussed. In particular, we note that specification of models that explicitly cannot accommodate or remove potential effects of hormesis may lead to biased potency estimates. Further, the presence of hormesis has implications for the design of toxicology experiments, with the spacing of concentration test conditions being critical.
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Cong, Menglong, Shun He, Jun Zhang, Chaoxi Luo, and Fuxing Zhu. "Hormetic Effects of Mixtures of Carbendazim and Iprodione on the Virulence of Botrytis cinerea." Plant Disease 103, no. 1 (January 2019): 95–101. http://dx.doi.org/10.1094/pdis-05-18-0754-re.
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Hormetic effects of fungicides on mycelial growth and virulence of plant pathogenic fungi have been reported, but the effects of fungicide mixtures on virulence hormesis of plant pathogens remain to be investigated. In this study, hormetic effects of mixtures of carbendazim and iprodione on the virulence of two carbendazim-resistant isolates of Botrytis cinerea were determined. Spraying carbendazim alone at 3 to 800 μg/ml exhibited hormetic effects on virulence to cucumber leaves, and carbendazim at 10 μg/ml had the maximum stimulation of 16.7% for isolate HBtom451. Spraying iprodione alone at 0.0001 to 0.0625 μg/ml exhibited hormetic effects on virulence, and iprodione at 0.025 μg/ml had the maximum stimulation of 18.7% for isolate HBtom451. However, spraying simultaneously carbendazim at 800 μg/ml and iprodione at 0.0625 μg/ml showed inhibitory effects on virulence to cucumber leaves. The mixture of carbendazim at 3 μg/ml and iprodione at 0.0001 μg/ml had much higher virulence stimulations than either fungicide at the same concentration alone. The maximum stimulation for the mixtures occurred at 10 and 0.0005 μg/ml for carbendazim and iprodione, respectively, and these concentrations were much lower than the concentration of their respective fungicide alone eliciting the maximum stimulations. The maximum stimulation amplitude for the mixture was slightly higher than that of each fungicide alone. These results demonstrated that carbendazim and iprodione mainly had dose-additive rather than amplitude-additive interactions when sprayed simultaneously with regard to virulence stimulations. Studies on virulence stimulations for mycelia treated with fungicide in potato dextrose agar showed that the maximum stimulation for the mixtures occurred at concentrations much lower than the concentration of carbendazim alone, indicating a dose-additive interaction when compared with carbendazim hormesis. Studies on potential physiological mechanisms of hormesis showed that increased tolerance to H2O2 may be one of the mechanisms for virulence hormesis for the mixtures of iprodione and carbendazim. These studies will advance our understanding of hormesis of fungicide mixtures.
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Rattan, Suresh I. S. "Physiological hormesis and hormetins in biogerontology." Current Opinion in Toxicology 29 (March 2022): 19–24. http://dx.doi.org/10.1016/j.cotox.2022.01.001.
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Kendig, Eric L., Hoa H. Le, and Scott M. Belcher. "Defining Hormesis: Evaluation of a Complex Concentration Response Phenomenon." International Journal of Toxicology 29, no. 3 (May 2010): 235–46. http://dx.doi.org/10.1177/1091581810363012.
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Hormesis describes dose-response relationships characterized by a reversal of response between low and high doses of chemicals, biological molecules, physical stressors, or other initiators of a response. Acceptance of hormesis as a viable dose-response theory has been limited until recently, in part, because of poor conceptual understanding, ad hoc and inappropriate use, and lack of a defined mechanism. By examining the history of this dose-response theory, it is clear that both pharmacological and toxicological studies provide evidence for hormetic dose responses, but retrospective examination of studies can be problematic at best. Limited scientific evidence and lack of a common lexicon with which to describe these responses have left hormesis open to inappropriate application to unrelated dose-response relationships. Future studies should examine low-dose effects using unbiased, descriptive criteria to further the scientific understanding of this dose response. A clear, concise definition is required to further the limited scientific evidence for hormetic dose responses.
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Rossnerova, Andrea, Alberto Izzotti, Alessandra Pulliero, Aalt Bast, S. I. S. Rattan, and Pavel Rossner. "The Molecular Mechanisms of Adaptive Response Related to Environmental Stress." International Journal of Molecular Sciences 21, no. 19 (September 25, 2020): 7053. http://dx.doi.org/10.3390/ijms21197053.
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The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as “hormesis”. Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.
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Calabrese, Edward J., and Wayne B. Jonas. "Homeopathy: Clarifying its relationship to hormesis." Human & Experimental Toxicology 29, no. 7 (June 17, 2010): 531–36. http://dx.doi.org/10.1177/0960327110369857.
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This paper presents the case that certain types of homeopathic medicine may represent a form of hormesis, that is, either pre- or post-conditioning hormesis. An example of a post-conditioning model by van Wijk and colleagues demonstrated successful enhancement of adaptive responses using below-toxic threshold doses (i.e. hormetic doses) of inducing agents when administered subsequent to a highly toxic chemical exposure, thus satisfying a basic experimental biomedical standard. Of note is that this model uses exposures within a measurable predicted hormetic range, unlike most forms of homeopathy. This experimental framework (along with a pre-conditioning model developed by Bellavite) provides a possible vehicle by which certain aspect(s) of homeopathy may be integrated into mainstream biomedical assessment and clinical practice.
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Aoishi, Yuka, Tatsuya Yoshimasu, Shoji Oura, Mitsumasa Kawago, Yoshimitsu Hirai, Miwako Miyasaka, Takuya Ohashi, and Yoshiharu Nishimura. "Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay." Dose-Response 17, no. 4 (October 1, 2019): 155932581989618. http://dx.doi.org/10.1177/1559325819896183.
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Purpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose–response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA). Methods: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other “special-type” cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose–response curve. Results: Hormesis was observed in 9 of the 22 cases; ED50 of cytotoxic effect was significantly higher ( P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 μg/mL). Conclusion: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel.
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Pickrell, J. A., and F. W. Oehme. "Examining the risks and benefits of considering both the traditional dose–response and hormesis in arriving at an acceptable exposure level." Human & Experimental Toxicology 25, no. 1 (January 2006): 23–27. http://dx.doi.org/10.1191/0960327106ht581oa.
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In examining traditional dose–response and hormesis, we have considered the case examples of pulmonary hyperplasia following inhalation of carbon black and pulmonary hyperplasia after methyleneindolenine (3MEIN) exposures, development of irreversible pulmonary fibrosis, effect of continuous exercise and low–level lead exposures, and colorectal cancer. Adaptation can be used to estimate conventional dose responses. All cases discussed provided increased information about the reactions if hormetic features were included. In only the shigatoxin case was there clear irrefutable evidence that beneficial hormetic properties exist and must be considered; however, the one–in–six advantage is too great to ignore the potential benefits of hormesis. We recommend such hormetic properties be considered together with conventional dose responses to improve estimates of chemical risk.
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Calabrese, Edward J. "Hormesis Mediates Acquired Resilience: Using Plant-Derived Chemicals to Enhance Health." Annual Review of Food Science and Technology 12, no. 1 (March 25, 2021): 355–81. http://dx.doi.org/10.1146/annurev-food-062420-124437.
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This review provides an assessment of hormesis, a highly conserved evolutionary dose-response adaptive strategy that leads to the development of acquired resilience within well-defined temporal windows. The hormetic-based acquired resilience has a central role in affecting healthy aging, slowing the onset and progression of numerous neurodegenerative and other age-related diseases, and reducing risks and damage due to heart attacks, stroke, and other serious conditions of public health and medical importance. The review provides the historical foundations of hormesis, its dose-response features, its capacity for generalization across biological models and endpoints measured, and its mechanistic foundations. The review also provides a focus on the adaptive features of hormesis, i.e., its capacity to upregulate acquired resilience and how this can be mediated by numerous plant-derived extracts, such as curcumin, ginseng, Ginkgo biloba, resveratrol, and green tea, that induce a broad spectrum of chemopreventive effects via hormesis.
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Nascarella, Marc A., Edward J. Stanek, George R. Hoffmann, and Edward J. Calabrese. "Quantification of Hormesis in Anticancer-Agent Dose-Responses." Dose-Response 7, no. 2 (February 4, 2009): dose—response.0. http://dx.doi.org/10.2203/dose-response.08-025.nascarella.
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Quantitative features of dose responses were analyzed for 2,189 candidate anticancer agents in 13 strains of yeast ( Saccharomyces cerevisiae). The agents represent a diverse class of chemical compounds including mustards, other alkylating agents, and antimetabolites, inter alia. Previous analyses have shown that the responses below the toxic threshold were stimulatory and poorly predicted by a threshold dose-response model, while better explained by a hormetic dose-response model. We determined the quantitative features of the hormetic concentration-responses ( n = 4,548) using previously published entry and evaluative criteria. The quantitative features that are described are: (1) the width of the concentration range showing stimulation above 10% of the control (mean of 5-fold), (2) the maximum stimulation of the concentration-responses (mean of 27% above the control), and (3) the width from the maximum stimulation to the toxicological threshold (mean of 3.7-fold). These results show that 52.5% of the 2,189 chemicals evaluated display hormetic concentration-responses in at least one of the 13 yeast strains. Many chemicals showed hormesis in multiple strains, and 24 agents showed hormesis in all 13 strains. The data are compared to previously reported quantitative features of hormesis based on published literature.
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Erofeeva, Elena A. "Plant hormesis and Shelford’s tolerance law curve." Journal of Forestry Research 32, no. 5 (March 18, 2021): 1789–802. http://dx.doi.org/10.1007/s11676-021-01312-0.
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AbstractShelford's law of tolerance is illustrated by a bell-shaped curve depicting the relationship between environmental factor/factors’ intensity and its favorability for species or populations. It is a fundamental basis of ecology when considering the regularities of environment impacts on living systems, and applies in plant biology, agriculture and forestry to manage resistance to environmental limiting factors and to enhance productivity. In recent years, the concept of hormesis has been increasingly used to study the dose–response relationships in living organisms of different complexities, including plants. This requires the need for an analysis of the relationships between the hormetic dose–response model and the classical understanding of plant reactions to environments in terms of Shelford's law of tolerance. This paper analyses various dimensions of the relationships between the hormetic model and Shelford’s tolerance law curve under the influence of natural environmental factors on plants, which are limiting for plants both in deficiency and excess. The analysis has shown that Shelford’s curve and hormetic model do not contradict but instead complement each other. The hormetic response of plants is localized in the stress zone of the Shelford’s curve when adaptive mechanisms are disabled within the ecological optimum. At the same time, in a species range, the ecological optimum is the most favorable combination of all or at least the most important environmental factors, each of which usually deviates slightly from its optimal value. Adaptive mechanisms cannot be completely disabled in the optimum, and hormesis covers optimum and stress zones. Hormesis can modify the plant tolerance range to environmental factors by preconditioning and makes limits of plant tolerance to environmental factors flexible to a certain extent. In turn, as a result of tolerance range evolution, quantitative characteristics of hormesis (width and magnitude of hormetic zone) as well as the range of stimulating doses, may significantly differ in various plant species and even populations and intra-population groups, including plants at different development stages. Using hormetic preconditioning for managing plant resistance to environmental limiting factors provides an important perspective for increasing the productivity of woody plants in forestry.
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Agathokleous, Evgenios, Mitsutoshi Kitao, and Edward J. Calabrese. "Biphasic effect of abscisic acid on plants: an hormetic viewpoint." Botany 96, no. 10 (October 2018): 637–42. http://dx.doi.org/10.1139/cjb-2018-0076.
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Abscisic acid (ABA) is a major phytohormone that regulates development and growth. Increasingly, the literature indicates that ABA enhances and inhibits a spectrum of plant responses within an hormetic-like biphasic dose–response manner. A recent extensive study on the response of a variety of Arabidopsis lines to ABA suggested the widespread occurrence of hormetic dose responses. Our independent reassessment of these data reveals the occurrence of more than 30 hormetic dose–response relationships with quantitative features fully consistent with the substantial and extensively assessed literature on plant hormesis. This analysis significantly extends earlier findings indicating that ABA mediates a broad spectrum of hormetic dose responses in plants. ABA-induced hormesis provides a novel framework for research with the potential to advance the current scientific bases of plant ecology, physiology, and toxicology and to enhance agricultural yields and productivity.
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Sandin, P. "The ethics of hormesis – no fuss?" Human & Experimental Toxicology 27, no. 8 (August 2008): 643–46. http://dx.doi.org/10.1177/0960327108098490.
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It has been argued that the phenomenon of hormesis should prompt us to revise current regulatory policy in order to take beneficial effects of small doses of various agents into account. I argue that three problems – the comparative smallness of hormetic effects, the fine-tuning problem, and the problem of aggregated actions – should lead us not to overemphasize the importance of hormesis for policy, and that they, if anything, points towards a non-consequentialist approach to the ethics of risk.
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Moffett, John R. "Miasmas, germs, homeopathy and hormesis: Commentary on the relationship between homeopathy and hormesis." Human & Experimental Toxicology 29, no. 7 (June 17, 2010): 539–43. http://dx.doi.org/10.1177/0960327110369855.
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Is hormesis related to homeopathy? Despite the superficial similarity of the low dose of the applied stimulus, there are compelling reasons for maintaining hormesis and homeopathy as unrelated. Homeopathy originated in the medical knowledge vacuum of the 19th century, prior to the acceptance of the germ/gene bases of disease. Homeopathy was never grounded on empirical scientific evidence. Hormesis, on the other hand, has always been an empirical science, involving properly controlled experiments. Hormesis is a concept in toxicology that involves biphasic dose responses in biological systems, wherein low doses of stressors can have beneficial effects and higher doses have harmful effects. Hormesis, as it applies to toxicology, is a necessary and useful concept describing adaptive organismic responses to applied stressors. Conversely, homeopathy is a medical doctrine based on the erroneous belief that substances which cause the symptoms of a disorder will cure the disorder when given to patients in small doses. To suggest that homeopathy is a form of post-exposure conditioning hormesis assumes that homeopathic practitioners employed the scientific method with measurable experimental end-points and proper controls, and that their ‘provings’ had actually determined the correct compound, at the correct dose, required to cure a disorder. Because many homeopathic preparations are diluted to a point where none of the starting solutes would likely remain, the idea of a beneficial or harmful hormetic dose becomes moot. Without supporting scientific evidence for the efficacy or purported mechanisms of homeopathy, the term hormesis should not be linked with it in any way.
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Sutou, Shizuyo, Akiko Koeda, Kana Komatsu, Toshiyuki Shiragiku, Hiroshi Seki, and Toshiyuki Kudo. "Collaborative Study of Thresholds for Mutagens: Hormetic Responses in Cell Proliferation Tests Using Human and Murine Lymphoid Cells." Dose-Response 19, no. 2 (April 1, 2021): 155932582110284. http://dx.doi.org/10.1177/15593258211028473.
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Background: We previously showed that hormetic responses can be established in cell activity tests using human and murine adherent cells. This time, we examined whether hormetic responses can be established in cell proliferation tests using suspended human and murine lymphoid cells. Methods: Human lymphoblastoid cells (TK6) and mouse lymphoma cells (L5178Y) were cultured in multi-well culture plates and treated with mitomycin C, ethyl methansulfonate, hygromycin B, aclarubicin or colchicine at various dose levels and the number of cells was measured at varied times using a flow cytometer. Results: When the ratio of the number of cells treated with a test chemical to those in the negative control was plotted, the dose-response relationship typically showed a reverse U-shaped curve, indicating the occurrence of hormesis and existence of thresholds in cell toxicity. The hormetic responses depended largely on the test chemical, dose level and exposure time. When examining responses over the course of time, a J-shaped or fallen S-shaped curve was also observed. Conclusions: The dose-response relationship showed a reverse U-shaped curve, a hallmark of hormesis, at least some time points for all chemicals tested here, indicating that chemical hormesis can be established in in vitro cell proliferation tests.
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Calabrese, Edward J. "Hormesis is central to toxicology, pharmacology and risk assessment." Human & Experimental Toxicology 29, no. 4 (March 23, 2010): 249–61. http://dx.doi.org/10.1177/0960327109363973.
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This paper summarizes numerous conceptual and experimental advances over the past two decades in the study of hormesis. Hormesis is now generally accepted as a real and reproducible biological phenomenon, being highly generalized and independent of biological model, endpoint measured and chemical class/physical stressor. The quantitative features of the hormetic dose response are generally highly consistent, regardless of the model and mechanism, and represent a quantitative index of biological plasticity at multiple levels of biological organization. The hormetic dose-response model has been demonstrated to make far more accurate predictions of responses in low dose zones than either the threshold or linear at low dose models. Numerous therapeutic agents widely used by humans are based on the hormetic dose response and its low dose stimulatory characteristics. It is expected that as low dose responses come to dominate toxicological research that risk assessment practices will incorporate hormetic concepts in the standard setting process.
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Hoffmann, GR, and WE Stempsey. "The hormesis concept and risk assessment: are there unique ethical and policy considerations?" Human & Experimental Toxicology 27, no. 8 (August 2008): 613–20. http://dx.doi.org/10.1177/0960327108098487.
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The hormesis concept holds that low doses of toxic substances and radiation elicit modest biological responses opposite to those caused by higher doses of the same agents. This concept stands in contrast to the prevailing views that a threshold model predicts most responses to toxicants at low doses and that linear extrapolation best predicts mutagenic and carcinogenic responses. Beyond the scientific considerations, there has been concern that inclusion of the hormesis model in risk assessment would raise complex ethical questions, pose serious challenges for policy makers, and threaten public safety. This article briefly reviews the growing evidence for hormesis and offers a perspective on the related ethical and societal issues. Complexities stem from the nature of biphasic curves, in which biological responses fall both above and below background levels. The monotonic responses of the threshold and linear models lend themselves to a single policy objective – avoiding harm associated with exposures. The biphasic responses of the hormesis model, however, suggest the possibility of accruing benefit as well as avoiding harm. The prospect of applying the hormesis model to public health policy is impeded by insufficient ability to identify the hormetic and toxic zones with precision. Moreover, heterogeneity among individuals in susceptibility to toxicants suggests that benefit and risk may be distributed unequally in the population. The potential shift in policy objectives associated with hormesis is considered relative to the difficulty of balancing the ethical principles of nonmaleficence and beneficence while maintaining a higher priority on the former.
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Jaworowski, Zbigniew. "Radiation hormesis - A remedy for fear." Human & Experimental Toxicology 29, no. 4 (March 23, 2010): 263–70. http://dx.doi.org/10.1177/0960327110363974.
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Personal reflections on radiation hormesis for the past 50 years are presented. The causes of ignoring and rejections of this phenomenon by international and national bodies and by radiation protection establishment are analyzed. The opposition against nuclear weapons and preparations for nuclear war was probably the main factor in inducing the concern for adverse effects of low doses of ionizing radiation, a byproduct of activism against the nuclear weapon tests. UNSCEAR was deeply involved in preparation of the scientific basis for cessation of nuclear test, and contributed to elaboration of the LNT assumption, which is in contradiction with the hormetic phenomenon. However, this authoritative body recognized also the existence of radiation hormesis, termed as ‘adaptive response.’ The political and vested interests behind exclusion of hormesis from the current risk assessment methodology are discussed.
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Tang, Sanyi, Juhua Liang, Changcheng Xiang, Yanni Xiao, Xia Wang, Jianhong Wu, Guoping Li, and Robert A. Cheke. "A general model of hormesis in biological systems and its application to pest management." Journal of The Royal Society Interface 16, no. 157 (August 2019): 20190468. http://dx.doi.org/10.1098/rsif.2019.0468.
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Hormesis, a phenomenon whereby exposure to high levels of stressors is inhibitory but low (mild, sublethal and subtoxic) doses are stimulatory, challenges decision-making in the management of cancer, neurodegenerative diseases, nutrition and ecotoxicology. In the latter, increasing amounts of a pesticide may lead to upsurges rather than declines of pests, ecological paradoxes that are difficult to predict. Using a novel re-formulation of the Ricker population equation, we show how interactions between intervention strengths and dose timings, dose–response functions and intrinsic factors can model such paradoxes and hormesis. A model with three critical parameters revealed hormetic biphasic dose and dose timing responses, either in a J-shape or an inverted U-shape, yielding a homeostatic change or a catastrophic shift and hormetic effects in many parameter regions. Such effects were enhanced by repeated pulses of low-level stimulations within one generation at different dose timings, thereby reducing threshold levels, maximum responses and inhibition. The model provides insights into the complex dynamics of such systems and a methodology for improved experimental design and analysis, with wide-reaching implications for understanding hormetic effects in ecology and in medical and veterinary treatment decision-making. We hypothesized that the dynamics of a discrete generation pest control system can be determined by various three-parameter spaces, some of which reveal the conditions for occurrence of hormesis, and confirmed this by fitting our model to both hormetic data from the literature and to a non-hormetic dataset on pesticidal control of mirid bugs in cotton.
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Hammitt, James K. "Economic implications of hormesis." Human & Experimental Toxicology 23, no. 6 (June 2004): 267–78. http://dx.doi.org/10.1191/0960327104ht447oa.
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The implications of hormesis for decision making about control of environmental exposures are examined. From an economic perspective, environmental exposures should be controlled to a level that optimizes health effects and minimizes control costs. The possibility that substances are, or may be, hormetic poses no fundamental challenge for economic analysis. In contrast with the linear no-threshold model, optimal control may be either less or more stringent under the hormetic model, depending on the incremental control cost. When exposure levels or exposure-response functions differ across individuals or are uncertain, the optimal population-level control of exposure must balance possible benefits and harms to individuals against control costs. Economic-incentive-based regulatory instruments, such as tradable permits, are likely to offer less improvement relative to command-and-control regulations under a hormetic model than under a linear no-threshold model.
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Agathokleous, Evgenios, and Mitsutoshi Kitao. "Ethylenediurea Induces Hormesis in Plants." Dose-Response 16, no. 2 (April 1, 2018): 155932581876528. http://dx.doi.org/10.1177/1559325818765280.
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Tropospheric ozone levels are elevated throughout the northern hemisphere. The potential threat of ozone to vegetation urges for studying plant protection methods. The chemical ethylenediurea (EDU) is the most extensively utilized substance for protecting plants against ozone damage in research projects. This commentary provides collective evidence showing hormetic responses of plants to EDU and suggests that EDU may act as a conditioning agent against elevated ozone exposures. This article also suggests testing different substances in a hormetic framework for protecting plants against ozone damage. The concept of hormesis provides a significant perspective for reducing the economic cost for plant protection.
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Calabrese, Edward J. "The Maturing of Hormesis as a Credible Dose-Response Model." Nonlinearity in Biology, Toxicology, Medicine 1, no. 3 (July 1, 2003): 154014203902499. http://dx.doi.org/10.1080/15401420390249907.
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Hormesis is a dose-response phenomenon that has received little recognition, credibility and acceptance as evidenced by its absence from major toxicological/risk assessment texts, governmental regulatory dose-response modeling for risk assessment, and non-visibility in major professional toxicological society national meetings. This paper traces the historical evolution of the hormetic dose-response hypothesis, why this model is not only credible but also more common than the widely accepted threshold model in direct comparative evaluation, and how the toxicological community made a critical error in rejecting hormesis, a rejection sustained over 70 years.
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Cook, Ralph, and Edward J. Calabrese. "The importance of hormesis to public health." Ciência & Saúde Coletiva 12, no. 4 (August 2007): 955–63. http://dx.doi.org/10.1590/s1413-81232007000400017.
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Hormesis is a specific type of nonmonotonic dose response whose occurrence has been documented across a broad range of biological models and diverse types of exposure. The effects that occur at various points along this curve can be interpreted as beneficial or detrimental, depending on the biological or ecologic context in which they occur. Because hormesis appears to be a relatively common phenomenon that has not yet been incorporated into regulatory practice, the objective of this commentary is to explore some of its more obvious public health and risk assessment implications, with particular reference to issues raised recently within this journal by other authors. Hormesis appears to be more common than doseresponse curves that are currently used in the risk assessment process. Although a number of mechanisms have been identified that explain many hormetic doseresponse relationships, better understanding of this phenomenon will likely lead to different strategies not only for the prevention and treatment of disease but also for the promotion of improved public health as it relates to both specific and more holistic health outcomes. We believe that ignoring hormesis is poor policy because it ignores knowledge that could be used to improve public health.
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Calabrese, Edward J., and Vittorio Calabrese. "Hormesis and Epidermal Stem Cells." Dose-Response 20, no. 3 (July 2022): 155932582211199. http://dx.doi.org/10.1177/15593258221119911.
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This paper provides an assessment of hormetic dose responses in epidermal stem cells (EpSCs) in animal models and humans, with emphasis on cell proliferation and differentiation and application to wound healing and aging processes. Hormetic dose responses were induced by several agents, including dietary supplements (eg, luteolin, quercetin), pharmaceuticals (eg, nitric oxide), endogenous agents (eg, growth/differentiation factor 5), and via diverse chemical means to sustain steaminess features to retard aging and disease onset. While hormetic dose responses have been extensively reported in a broad spectrum of stem cells, this area has only been explored to a limited extent in EpSCs, principally within the past 5 years. Nonetheless, these findings provide the first integrated assessment of hormesis and EpSC biology within the context of enhancing key functions such as cell proliferation and differentiation and resilience to inflammatory stresses. This paper assesses putative mechanisms of hormetic responses in EpSCs and potential therapeutic applications to prevent dermatological injury and disease.
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Kafi, Zahra, Hamid Cheshomi, and Omid Gholami. "7-Isopenthenyloxycoumarin, Arctigenin, and Hesperidin Modify Myeloid Cell Leukemia Type-1 (Mcl-1) Gene Expression by Hormesis in K562 Cell Line." Dose-Response 16, no. 3 (July 1, 2018): 155932581879601. http://dx.doi.org/10.1177/1559325818796014.
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Hormesis is a new concept in dose–response relationship. Despite of traditional dose–response curves, there is a low-dose stimulation and a high-dose inhibition in this case. Hormesis effect in apoptosis induction/inhibition by natural compounds is reported previously. Here, we searched this effect for myeloid cell leukemia type-1 (Mcl-1) gene expression by phytochemicals 7-isopenthenyloxycoumarin (7-IP), arctigenin (Arg), and hesperidin (Hsp). For this purpose, first we tested the cytotoxicity of various doses of these compounds against K562 leukemia cell lines for different times by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. After that we explored the effect of various doses of these phytochemicals on Mcl-1 gene expression for different times by real-time polymerase chain reaction method. We found that these phytochemicals have cytotoxicity against K562 cell line. Hesperidin is the most cytotoxic agent. We also found that these natural compounds have hormetic effect on Mcl-1 gene expression. The hormetic model in Mcl-1 gene expression is overcompensation stimulation. This phenomenon is reported for the first time. We conclude that 7-IP, Arg, and Hsp are cytotoxic against K562 cancerous cells and induce/inhibit Mcl-1 gene expression by hormesis dose–response relationship.
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Shephard, Alexander M., Vadim Aksenov, Jonathan Tran, Connor J. Nelson, Douglas R. Boreham, and C. David Rollo. "Hormetic Effects of Early Juvenile Radiation Exposure on Adult Reproduction and Offspring Performance in the Cricket (Acheta domesticus)." Dose-Response 16, no. 3 (July 1, 2018): 155932581879749. http://dx.doi.org/10.1177/1559325818797499.
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Exposure to low-dose ionizing radiation can have positive impacts on biological performance—a concept known as hormesis. Although radiation hormesis is well-documented, the predominant focus has been medical. In comparison, little research has examined potential effects of early life radiation stress on organismal investment in life history traits that closely influence evolutionary fitness (eg, patterns of growth, survival, and reproduction). Evaluating the fitness consequences of radiation stress is important, given that low-level radiation pollution from anthropogenic sources is considered a major threat to natural ecosystems. Using the cricket ( Acheta domesticus), we tested a wide range of doses to assess whether a single juvenile exposure to radiation could induce hormetic benefits on lifetime fitness measures. Consistent with hormesis, we found that low-dose juvenile radiation positively impacted female fecundity, offspring size, and offspring performance. Remarkably, even a single low dose of radiation in early juvenile development can elicit a range of positive fitness effects emerging over the life span and even into the next generation.
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Catlin, Robert J. "Hormesis." Science 246, no. 4928 (October 20, 1989): 311. http://dx.doi.org/10.1126/science.246.4928.311.b.
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CATLIN, R. J. "Hormesis." Science 246, no. 4928 (October 20, 1989): 311. http://dx.doi.org/10.1126/science.246.4928.311-a.
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Calabrese, EJ, I. Iavicoli, and V. Calabrese. "Hormesis." Human & Experimental Toxicology 32, no. 2 (October 11, 2012): 120–52. http://dx.doi.org/10.1177/0960327112455069.
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Jargin, SV. "Hormesis." Human & Experimental Toxicology 34, no. 4 (March 25, 2015): 439–41. http://dx.doi.org/10.1177/0960327114564796.
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Matus, Soledad, Karen Castillo, and Claudio Hetz. "Hormesis." Autophagy 8, no. 6 (June 23, 2012): 997–1001. http://dx.doi.org/10.4161/auto.20748.
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Calabrese, E. J., and L. A. Baldwin. "Chemical hormesis: its historical foundations as a biological hypothesis." Human & Experimental Toxicology 19, no. 1 (January 2000): 2–31. http://dx.doi.org/10.1191/096032700678815585.
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Despite the long history of hormesis-related experimental research no systematic effort to describe its early history has been undertaken. The present paper attempts to reconstruct and assess the early history of such research and to evaluate how advances in related scientific fields affected the course of hormesis-related research. The purpose of this paper is not only to satisfy this gap in current knowledge, but also to provide a foundation for the assessment of how the concept of hormetic dose-response relationships may have affected the nature of the bioassay especially with respect to hazard assessment practices within a modern risk assessment Eramework.