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Edward J Calabrese

Publications and source records attributed to Edward J Calabrese.

31 records · Page 2Linked to original sources
PubMed2003

Chemotherapeutics and hormesis.

This article represents the first comprehensive assessment of hormetic effects of chemotherapeutic agents. Hormetic dose-response relationships were reported for a wide range of chemotherapeutics, including antibiotics, antiviral, and antitumor agents as well as substances that affect hair growth, prostate function, cognitive performance, and numerous other endpoints. Particular attention was given to assessing the quantitative features of the dose response, the underlying mechanistic features of the biphasic nature of the dose response, and the clinical implications of hormetic responses. Recognition of the hormetic-like biphasic nature of the dose response is expected to have an important impact on the design of experiments to assess chemotherapeutics and how such agents may be employed more successfully in clinical applications.

Animals↗
PubMed2003

Peptides and hormesis.

The article provides a broad assessment of the occurrence of hormetic-like biphasic dose-response relationships by over 30 peptides representing many major peptide classes. These peptide-induced biphasic dose responses were observed to occur in a extensive range of tissues, affecting an diverse range of biological endpoints. Despite diversity of peptides, models and endpoints, the quantitative features of the biphasic dose responses are remarkably similar with respect to the amplitude and width of the stimulatory response. These findings strongly suggest that hormetic-like biphasic dose responses represent a broadly generalizable biological phenomenon.

Animals↗
PubMed2003

Ethanol and hormesis.

This article provides a detailed assessment of the toxicological and pharmacological literature concerning alcohol-induced biphasic dose-response relationships. The assessment reveals that alcohol-induced hormetic-like dose-response relationships are commonly observed, highly generalizeable according to model and endpoint and quantitative feature of the dose response. These findings have important implications affecting study design, animal model, and endpoint selection as well as clinical applications.

Animals↗
PubMed2003

The hormetic dose-response model is more common than the threshold model in toxicology.

The threshold dose-response model is widely viewed as the most dominant model in toxicology. The present study was designed to test the validity of the threshold model by assessing the responses of doses below the toxicological NOAEL (no observed adverse effect level) in relationship to the control response (i.e., unexposed group). Nearly 1,800 doses below the NOAEL, from 664 dose-response relationships derived from a previously published database that satisfied a priori entry criteria, were evaluated. While the threshold model predicts a 1:1 ratio of responses "greater than" to "less than" the control response (i.e., a random distribution), a 2.5:1 ratio (i.e., 1171:464) was observed, reflecting 31% more responses above the control value than expected (p < 0.0001). The mean response (calculated as % control response) of doses below the NOAEL was 115.0% +/- 1.5 standard error of the mean (SEM). These findings challenge the long-standing belief in the primacy of the threshold model in toxicology (and other areas of biology involving dose-response relationships) and provide strong support for the hormetic-like biphasic dose-response model characterized by a low-dose stimulation and a high-dose inhibition. These findings may affect numerous aspects of toxicological and biological/biomedical research related to dose-response relationships, including study design, risk assessment, as well as chemotherapeutic strategies.

Animals↗
PubMed2002

Hormesis: the dose-response revolution.

Hormesis, a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition, has been frequently observed in properly designed studies and is broadly generalizable as being independent of chemical/physical agent, biological model, and endpoint measured. This under-recognized and -appreciated concept has the potential to profoundly change toxicology and its related disciplines with respect to study design, animal model selection, endpoint selection, risk assessment methods, and numerous other aspects, including chemotherapeutics. This article indicates that as a result of hormesis, fundamental changes in the concept and conduct of toxicology and risk assessment should be made, including (a) the definition of toxicology, (b) the process of hazard (e.g., including study design, selection of biological model, dose number and distribution, endpoint measured, and temporal sequence) and risk assessment [e.g., concept of NOAEL (no observed adverse effect level), low dose modeling, recognition of beneficial as well as harmful responses] for all agents, and (c) the harmonization of cancer and noncancer risk assessment.

Animals↗
PubMed2002

Hormesis and high-risk groups.

The concept of hormesis (i.e., biological phenomena characterized by dose-response relationships displaying low-dose stimulation and high-dose inhibition) has important implications for current risk assessment practices because of its generalizability with respect to experimental model, agent, and endpoint measured. This paper addresses the question of whether hormesis is present in high-risk subpopulations and highly susceptible species. Evaluation of published data revealed that hormetic dose-response relationships occur with similar quantitative characteristics among species and individuals that display widely differing susceptibility to various toxicants. This observation suggests that the cause of the differential susceptibility in the more susceptible organisms is not due to the absence of the hormetic response but to some other factor(s). However, despite the recognition that hormetic responses are common and similar in susceptible and resistant organisms there are sufficient examples indicating that some strains/individuals may lack the capacity to produce the low-dose stimulatory response. Thus, the capacity to display hormetic effects is one of a variety of factors affecting differential susceptibility to xenobiotics and needs to be addressed within the hazard assessment process.

Age Factors↗
PubMed2002

Applications of hormesis in toxicology, risk assessment and chemotherapeutics.

There is much debate over the fundamental shape of the dose-response curve in the low-dose zone, particularly in the fields of toxicology and risk assessment. The defaults, principally accepted dose-response models in the major texts in these areas and in government regulatory activities, are a threshold model for non-carcinogens and a linear model for most carcinogens. We have argued that in properly designed studies the U-shaped hormetic response predominates and is more fundamental. In this article, a broad range of basic issues associated with the acceptance of U-shaped dose responses as central to toxicology, pharmacology and their applications to risk assessment and medicine will be discussed.

Animals↗
PubMed2002

Hormesis: changing view of the dose-response, a personal account of the history and current status.

This paper provides a personal account of the history of the hormesis concept, and of the role of the dose response in toxicology and pharmacology. A careful evaluation of the toxicology and pharmacology literatures suggests that the biphasic dose response that characterizes hormesis may be much more widespread than is commonly recognized, and may come to rival our currently favored ideas about toxicological dose responses confined to the linear and threshold representations used in risk assessment. Although hormesis-like biphasic dose responses were already well-established in chemical and radiation toxicology by the early decades of the 20th century, they were all but expunged from mainstream toxicology in the 1930s. The reasons may be found in a complex set of unrelated problems of which difficulties in replication of low-dose stimulatory responses resulting from poor study designs, greater societal interest in high-dose effects, linking of the concept of hormesis to the practice of homeopathy, and perhaps most crucially a complete lack of strong leadership to advocate its acceptance in the right circles. I believe that if hormesis achieves widespread recognition as a valid and valuable interpretation of dose-response results, we would expect an increase in the breadth of evaluations of the dose-response relationship which could be of great value in hazard and risk assessment as well as in future approaches to drug development and/or chemotherapeutics.

Animals↗
PubMedDate not supplied

Hormetic dose-response relationships in immunology: occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications.

This article provides an assessment of the occurrence of immune-system-related hormetic-like biphasic dose-response relationships. Such dose-response relationships are extensive, with over 90 different immune response-related endpoints reported, induced by over 70 endogenous agonists, over 100 drugs, and over 40 environmental contaminants. Such hormetic responses were reported in over 30 animal models, over a dozen mammalian and human cell lines. These findings demonstrate that immune-system-related hormetic-like biphasic dose-response relationships are common and highly generalizable according to model, endpoint, and chemical class. The quantitative features of the dose response are generally consistent with previously published examples of hormetic dose responses for other biological endpoints. These findings were generally recognized and explicitly discussed by the original authors, often with consideration given to possible mechanistic foundations as well as numerous clinical implications. Despite the recognition by individual authors of the hormetic nature of these observed responses, the overall widespread nature of immune-related hormetic responses has been only little appreciated, with a general lack of insight into the highly generalizable nature of this phenomenon as well as the complex regulatory networks affecting biological switching mechanisms that result in the hormetic responses.

Adaptation, Physiological↗
PubMedDate not supplied

Hormesis--basic, generalizable, central to toxicology and a method to improve the risk-assessment process.

Hormesis, a dose-response phenomenon characterized by a low-dose stimulation and a high-dose inhibition, has been the object of controversy due to its challenging of basic understandings of the dose-response relationship and implications for risk assessment. The author addresses issues relating to the definition of hormesis, the relationship of hormesis to risk assessment and risk management, and the generalizability of hormesis within the toxicological literature.

Dose-Response Relationship, Drug↗