Calabrese, Edward

Job Title

Professor, Environmental Health Sciences

Last Name

Calabrese

First Name

Edward

Expertise

emphasis on biological factors (i.e. genetic and nutritional factors) which enhance susceptibility to pollutant toxicity
environmental toxicology

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Now showing 1 - 9 of 9

Session G1: Plenary Session: Nuclear Power and Climate Change - When Sciences Fails Society: Toxicology's 20th Century Legacy
(2011-11-19) Calabrese, Edward J
This presentation provides an assessment of hormesis, a dose-response concept that is characterized by a low-dose stimulation and a high-dose inhibition. It will trace the historical foundations of hormesis, its quantitative features and mechanistic foundations, and its risk assessment implications. It will be argued that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations used by regulatory agencies such as the EPA and FDA. The hormetic dose response is highly generalizable, being independent of biological model, endpoint measured, chemical class, physical agent (e.g., radiation) and inter-individual variability. Hormesis also provides a framework for the study and assessment of chemical mixtures, incorporating the concept of additivity and synergism. Because the hormetic biphasic dose response represents a general pattern of biological responsiveness, it is expected that it will become progressively more significant within toxicological evaluation and chemical and radiation risk assessment practices as well as having numerous biomedical applications. Particular application will be directed towards how hormesis may affect the risk assessment process for chemicals and ionizing radiation.
Welcome to Nonlinearity in Biology, Toxicology and Medicine
Calabrese, Edward J.
Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models
(2020-01-01) Rosa, Gabriele Di; Brunetti, Givovanni; Scuto, Maria; Salinaro, Angela Trovato; Calabrese, Edward; Crea, Roberto; Schmitz-Linneweber, Christian; Calabrese, Vittorio; Saul, Nadine
Parkinson’s disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its “natural” environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.
Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects
(2020-01-01) Calabrese, Edward
This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer’s and Parkinson’s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications.
A glance into how the cold war and governmental loyalty investigations came to affect a leading U.S. radiation geneticist: Lewis J. Stadler’s nightmare
(2017-01-01) Calabrese, Edward J.
This paper describes an episode in the life of the prominent plant radiation geneticist, Lewis J. Stadler (1897–1954) during which he became a target of the Federal Bureau of Investigation (FBI) concerning loyalty to the United States due to possible associations with the communist party. The research is based on considerable private correspondence of Dr. Stadler, the FBI interrogatory questions and Dr. Stadler’s answers and letters of support for Dr. Stadler by leading scientists such as, Hermann J. Muller.
Does the root to shoot ratio show a hormetic response to stress? An ecological and environmental perspective
(2019-01-01) Agathokleous, Evgenios; Belz, Regina G.; Kitao, Mitsutoshi; Koike, Takayoshi; Calabrese, Edward J.
Root/shoot (R/S) ratio is an important index for assessing plant health, and has received increased attention in the last decades as a sensitive indicator of plant stress induced by chemical or physical agents. The R/S ratio has been discussed in the context of ecological theory and its potential importance in ecological succession, where species follow different strategies for above-ground growth for light or below-ground competition for water and nutrients. We present evidence showing the R/S ratio follows a biphasic dose–response relationship under stress, typical of hormesis. The R/S ratio in response to stress has been widely compared among species and ecological succession classes. It is constrained by a variety of factors such as ontogeny. Furthermore, the current literature lacks dose–response studies incorporating the full dose–response continuum, hence limiting scientific understanding and possible valuable application. The data presented provide an important perspective for new-generation studies that can advance current ecological understanding and improve carbon storage estimates by R/S ratio considerations. Hormetic response of the R/S ratio can have an important role in forestry for producing seedlings with desired characteristics to achieve maximum health/productivity and resilience under plantation conditions.
Session G: Nuclear Power/Climate Change – When Sciences Fails Society: Toxicology’s 20th Century Legacy
(2011-11-19) Calabrese, Edward J
This presentation provides an assessment of hormesis, a dose-response concept that is characterized by a low-dose stimulation and a high-dose inhibition. It will trace the historical foundations of hormesis, its quantitative features and mechanistic foundations, and its risk assessment implications. It will be argued that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations used by regulatory agencies such as the EPA and FDA. The hormetic dose response is highly generalizable, being independent of biological model, endpoint measured, chemical class, physical agent (e.g., radiation) and inter-individual variability. Hormesis also provides a framework for the study and assessment of chemical mixtures, incorporating the concept of additivity and synergism. Because the hormetic biphasic dose response represents a general pattern of biological responsiveness, it is expected that it will become progressively more significant within toxicological evaluation and chemical and radiation risk assessment practices as well as having numerous biomedical applications. Particular application will be directed towards how hormesis may affect the risk assessment process for chemicals and ionizing radiation.
The Emergence of the Dose–Response Concept in Biology and Medicine
(2016-01-01) Calabrese, Edward J.
A historical assessment of the origin of the dose–response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e., hormetic) dose–response models emerged in the late 19th and early 20th centuries and competed for acceptance and dominance. Particular attention is directed to the hormetic model for which a general description and evaluation is provided, including its historical basis, and how it was marginalized by the medical and pharmacology communities in the early decades of the 20th century.
Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis
(2020-01-01) Calabrese, Vittorio; Scuto, maria; Salinao, Angela Trovato; Dionisio, Giuseppe; Modafferi, Sergio; Ontario, Maria Laura; Greco, Valentina; Sciuto, Sebastiano; Schmitt, Claus Peter; Calabrese, Edward; Peters, Verena
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans.