600 results on '"Calabrese EJ"'
Search Results
2. Funding trends in hormetic research
- Author
-
Cottrell, MA, primary, Mills, WA, additional, and Calabrese, EJ, additional
- Published
- 2019
- Full Text
- View/download PDF
3. Peroxisome Proliferation as an Epigenetic Mechanism of Carcinogenesis: Relevance to Aquatic Toxicology
- Author
-
Yang, J-H, primary, Kostecki, PT, additional, and Calabrese, EJ, additional
- Published
- 1990
- Full Text
- View/download PDF
4. Originator of the hormesis concept: Rudolf Virchow or Hugo Schulz
- Author
-
Calabrese, EJ, primary
- Published
- 2017
- Full Text
- View/download PDF
5. Osteoporosis and Alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling
- Author
-
Cornelius, C, Koverech, G, Crupi, Rosalia, Di Paola, R, Koverech, A, Lodato, F, Scuto, M, Salinaro, At, Cuzzocrea, Salvatore, Calabrese, Ej, Calabrese, V., and DI PAOLA, Rosanna
- Subjects
Pathology ,medicine.medical_specialty ,redox status ,Cellular homeostasis ,Review Article ,medicine.disease_cause ,Neuroprotection ,Bone remodeling ,Alzheimer's disease, Cellular stress response, Hormesis, Oxidative stress, Redox status, Vitagenes ,hormesis ,Cellular stress response ,Heat shock protein ,medicine ,oxidative stress ,Pharmacology (medical) ,Pharmacology ,cellular stress response ,biology ,lcsh:RM1-950 ,Alzheimer's disease ,lcsh:Therapeutics. Pharmacology ,Sirtuin ,biology.protein ,vitagenes ,Thioredoxin ,Alzheimer’s disease ,Oxidative stress - Abstract
Alzheimer’s disease (AD) as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL)-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on aging processes.
- Published
- 2014
6. Cellular Stress Response, Hormesis, and Vitagens in Aging and Longevity: Role of mitochondrial 'Chi'
- Author
-
Cornelius, C, Graziano, A, Perrotta, ROSARIO EMANUELE, Paola, Rd, Cuzzocrea, S, Calabrese, Ej, and Calabrese, Vittorio
- Subjects
Redox balance ,Free radicals ,mitochondrial medicine - Published
- 2013
7. Historical use of x-rays
- Author
-
Calabrese, EJ, primary and Dhawan, G, additional
- Published
- 2013
- Full Text
- View/download PDF
8. Hormesis
- Author
-
Calabrese, EJ, primary, Iavicoli, I, additional, and Calabrese, V, additional
- Published
- 2012
- Full Text
- View/download PDF
9. Hormesis, non-linearity, and risk communication
- Author
-
Calabrese, EJ, primary
- Published
- 2009
- Full Text
- View/download PDF
10. Hormesis and ethics: introduction
- Author
-
Calabrese, EJ, primary
- Published
- 2008
- Full Text
- View/download PDF
11. Effects of sub-chronic exposure to palladium (as potassium hexachloro-palladate) on cytokines in male Wistar rats
- Author
-
Iavicoli, I, primary, Carelli, G, additional, Marinaccio, A, additional, Fontana, L, additional, and Calabrese, EJ, additional
- Published
- 2008
- Full Text
- View/download PDF
12. Letter to the Editor
- Author
-
Calabrese Ej
- Subjects
Pharmacology ,chemistry.chemical_compound ,chemistry ,business.industry ,Phalloidin ,Immunology ,Medicine ,Lethality ,Mononuclear phagocyte system ,Toxicology ,business ,Function (biology) - Published
- 1996
13. Historical use of x-rays: Treatment of inner ear infections and prevention of deafness.
- Author
-
Calabrese, EJ and Dhawan, G
- Subjects
- *
EAR infections , *OTITIS media , *RADIOTHERAPY , *LYMPHADENITIS , *TWENTIETH century - Abstract
The article discusses the role of radiotherapy in the treatment of inner ear infections in the medical community in the first half of the 20th century. Topics discussed include clinical features of Otitis Media (OM), mastoiditis and cervical lymphadenitis, efficacy of x-ray in treating these clinical conditions and mechanistic basis of the clinical successes of treatment.
- Published
- 2014
- Full Text
- View/download PDF
14. Letter
- Author
-
Calabrese Ej and Baldwin La
- Subjects
medicine.medical_specialty ,business.industry ,Family medicine ,medicine ,Cancer ,Harmonization ,Toxicology ,medicine.disease ,business ,Risk assessment - Published
- 2001
15. Introduction
- Author
-
Calabrese, EJ, primary
- Published
- 1998
- Full Text
- View/download PDF
16. A Toxicological Basis to Derive a Generic Interspecies Uncertainty Factor.
- Author
-
Calabrese, EJ, primary and Baldwin, LA, additional
- Published
- 1994
- Full Text
- View/download PDF
17. Hormesis: Its impact on medicine and health.
- Author
-
Calabrese, EJ, Iavicoli, I, and Calabrese, V
- Subjects
- *
HORMESIS , *PHARMACEUTICAL industry , *PUBLIC health , *THERAPEUTICS , *PHYSICIANS - Abstract
This article offers a broad assessment of the hormetic dose response and its relevance to biomedical researchers, physicians, the pharmaceutical industry, and public health scientists. This article contains a series of 61 questions followed by relatively brief but referenced responses that provides support for the conclusion that hormesis is a reproducible phenomenon, commonly observed, with a frequency far greater than other dose–response models such as the threshold and linear nonthreshold dose–response models. The article provides a detailed background information on the historical foundations of hormesis, its quantitative features, mechanistic foundations, as well as how hormesis is currently being used within medicine and identifying how this concept could be further applied in the development of new therapeutic advances and in improved public health practices. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
- Full Text
- View/download PDF
18. Defining Hormesis.
- Author
-
Calabrese, EJ and Baldwin, LA
- Subjects
- *
HORMESIS , *RISK assessment , *TOXICOLOGY - Abstract
Much confusion surrounds the concept of hormesis and what its biological meaning represents. This paper provides a definition of hormesis that addresses its historical foundations, quantitative features, and underlying evolutionary and toxicologically based mechanistic strategies. Hormesis should be considered an adaptive response characterized by biphasic dose responses of generally similar quantitative features with respect to amplitude and range of the stimulatory response that are either directly induced or the result of compensatory biological processes following an initial disruption in homeostasis. Given the limited magnitude of the stimulatory response (i.e., usually 30-60% greater than controls at maximum), heightened study design and replication requirements are often necessary to ensure reliable judgments on causality. Even though hormesis is considered an adaptive response, the issue of beneficial/harmful effects should not be part of the definition of hormesis, but reserved to a subsequent evaluation of the biological and ecological context of the response. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
19. Soil ingestion: a concern for acute toxicity in children.
- Author
-
Calabrese EJ, Stanek EJ, James RC, and Roberts SM
- Abstract
Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the U.S. Environmental Protection Agency (U.S. EPA) has assumed that 95 percent of children ingest 200 mg of soil per day or less for exposure assessment purposes, some children have been observed to ingest up to 25 to 60 g of soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from contaminant concentrations U.S. EPA regards as representing conservative screening values (i.e., U.S. EPA soil screening levels and U.S. EPA Region III risk-based concentrations for residential soils). For a set of 13 chemicals included in the analysis, contaminant doses resulting from a one-time soil pica episode (5 to 50 g of soil ingested) were compared with acute dosages shown to produce toxicity in humans in clinical studies or case reports. For four of these chemicals, a soil pica episode was found to result in a contaminant dose approximating or exceeding the acute human lethal dose. For five of the remaining chemicals, the contaminant dose from a soil pica episode was well within the reported dose range in humans for toxicity other than lethality. Because both the exposure episodes and the toxicological response information are derived from observations in humans, these findings are regarded as particularly relevant for human health risk assessment. They suggest that, for some chemicals, ostensibly conservative soil criteria based on chronic exposure using current U.S. EPA methodology may not be protective of children during acute soil pica episodes. [ABSTRACT FROM AUTHOR]
- Published
- 1999
20. Response to expert commentators.
- Author
-
Calabrese, EJ and Baldwin, LA
- Subjects
- *
HORMESIS , *RISK assessment - Abstract
Comments on studies on the role of hormesis in the field of toxicology and risk assessment.
- Published
- 2002
- Full Text
- View/download PDF
21. Part 1. The role of ROS in health disease: Part 2. Proposing a definition of hormesis.
- Author
-
Calabrese, EJ
- Subjects
- *
REACTIVE oxygen species , *HORMESIS - Abstract
Introduces articles on the role of reactive oxygen species and on the definition of hormesis.
- Published
- 2002
- Full Text
- View/download PDF
22. Hormetic dose responses induced by antibiotics in bacteria: A phantom menace to be thoroughly evaluated to address the environmental risk and tackle the antibiotic resistance phenomenon
- Author
-
Mauro Fedele, Carolina Santocono, Edward J. Calabrese, Francesco Flaviano Russo, Evgenios Agathokleous, Ivo Iavicoli, Luca Fontana, Ilaria Vetrani, Iavicoli, I, Fontana, L, Agathokleous, E, Santocono, C, Russo, F, Vetrani, I, Fedele, M, and Calabrese, Ej
- Subjects
Hormesis, Subinhibitory concentrations, Antimicrobial resistance, Plasmid conjugative transfer, Mixture toxicology ,Environmental Engineering ,Bacteria ,biology ,medicine.drug_class ,Mechanism (biology) ,Antibiotics ,Biofilm ,Hormesis ,Drug Resistance, Microbial ,biology.organism_classification ,Pollution ,Anti-Bacterial Agents ,Plasmid ,Antibiotic resistance ,Environmental risk ,Immunology ,medicine ,Humans ,Environmental Chemistry ,Waste Management and Disposal ,Ecosystem - Abstract
The environmental contamination of antibiotics caused by their over or inappropriate use is a major issue for environmental and human health since it can adversely impact the ecosystems and promote the antimicrobial resistance. Indeed, considering that in the environmental matrices these drugs are present at low levels, the possibility that bacteria exhibit a hormetic response to increase their resilience when exposed to antibiotic subinhibitory concentrations might represent a serious threat. Information reported in this review showed that exposure to different types of antibiotics, either administered individually or in mixtures, is capable of exerting hormetic effects on bacteria at environmentally relevant concentrations. These responses have been reported regardless of the type of bacterium or antibiotic, thus suggesting that hormesis would be a generalized adaptive mechanism implemented by bacteria to strengthen their resistance to antibiotics. Hormetic effects included growth, bioluminescence and motility of bacteria, their ability to produce biofilm, but also the frequency of mutation and plasmid conjugative transfer. The evaluation of quantitative features of antibiotic-induced hormesis showed that these responses have both maximum stimulation and dose width characteristics similar to those already reported in the literature for other stressors. Notably, mixtures comprising individual antibiotic inducing stimulatory responses might have distinct combined effects based on antagonistic, synergistic or additive interactions between components. Regarding the molecular mechanisms of action underlying the aforementioned effects, we put forward the hypothesis that the adoption of adaptive/defensive responses would be driven by the ability of antibiotic low doses to modulate the transcriptional activity of bacteria. Overall, our findings suggest that hormesis plays a pivotal role in affecting the bacterial behavior in order to acquire a survival advantage. Therefore, a proactive and effective risk assessment should necessarily take due account of the hormesis concept to adequately evaluate the risks to ecosystems and human health posed by antibiotic environmental contamination.
- Published
- 2021
23. Transgenerational hormesis in healthy aging and antiaging medicine from bench to clinics: Role of food components.
- Author
-
Calabrese V, Osakabe N, Siracusa R, Modafferi S, Di Paola R, Cuzzocrea S, Jacob UM, Fritsch T, Abdelhameed AS, Rashan L, Wenzel U, Franceschi C, and Calabrese EJ
- Subjects
- Humans, Animals, Healthy Aging metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases drug therapy, Hormesis
- Abstract
Neurodegenerative diseases have multifactorial pathogenesis, mainly involving neuroinflammatory processes. Finding drugs able to treat these diseases, expecially because for most of these diseases there are no effective drugs, and the current drugs cause undesired side effects, represent a crucial point. Most in vivo and in vitro studies have been concentrated on various aspects related to neurons (e.g. neuroprotection), however, there has not been focus on the prevention of early stages involving glial cell activation and neuroinflammation. Recently, it has been demonstrated that nutritional phytochemicals including polyphenols, the main active constituents of the Mediterranean diet, maintain redox balance and neuroprotection through the activation of hormetic vitagene pathway. Recent lipidomics data from our laboratory indicate mushrooms as strong nutritional neuronutrients with strongly activity against neuroinflammation in Meniere' diseaseas, a model of cochleovestibular neural degeneration, as well as in animal model of traumatic brain injury, or rotenone induced parkinson's disease. Moreover, Hidrox®, an aqueous extract of olive containing hydroxytyrosol, and Boswellia, acting as Nrf2 activators, promote resilience by enhancing the redox potential, and thus, regulate through hormetic mechanisms, cellular stress response mechanisms., Thus, modulation of cellular stress pathways, in particular vitagenes system, may be an innovative approach for therapeutic intervention in neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
- Full Text
- View/download PDF
24. Newly discovered letter: why Muller failed to cite the negative mouse mutation findings of Snell, preserving his chances to receive the Nobel Prize.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Animals, Mice, History, 20th Century, Humans, Nobel Prize, Mutation
- Abstract
A recently acquired letter between Hermann Muller and his wife (March 21, 1933) reveals that Muller had learned that he had been nominated for the Nobel Prize in 1932 with about 1/3 of the total votes being supportive. Muller was hopeful that over time sufficient votes would lead to receiving the award. The knowledge of Muller on this matter and its timing provide a likely explanation why Muller never cited the negative mouse mutation findings of George Snell, performed under Muller's direction during that time period. This action of Muller, along with the failure of Snell to promote his discovery, greatly reduced the chances that those findings would complicate his attempt to garner support for his LNT single-hit model and its application to hereditary and cancer risk assessment. It also helped Muller achieve the Nobel Prize, allowing him the necessary international visibility to promote his ideologically driven ionizing radiation-related LNT-based paradigm., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
25. Reimagining agrochemical pollution mitigation: Leveraging hormesis for sustainable environmental solutions.
- Author
-
Agathokleous E, Guedes RNC, and Calabrese EJ
- Subjects
- Environmental Restoration and Remediation methods, Hormesis, Agrochemicals, Environmental Pollution prevention & control
- Abstract
Emerging evidence reveals that low doses of stress stimulate, and high doses suppress, organism responses - a phenomenon known as hormesis. Here, we propose a framework for harnessing hormesis principles to optimize agrochemical use and mitigate pollution. We discuss how hormesis can be applied in agrochemical context and highlight challenges and needs beyond scientific research, offering a perspective for sustainable environmental solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
26. Oocyte maturation, blastocyst and embryonic development are mediated and enhanced via hormesis.
- Author
-
Calabrese EJ, Pressman P, Hayes AW, Dhawan G, Kapoor R, Agathokleous E, and Calabrese V
- Subjects
- Humans, Animals, Female, Hormesis, Oocytes drug effects, Oocytes physiology, Embryonic Development drug effects, Blastocyst drug effects, Blastocyst physiology
- Abstract
The present paper provides the first integrative assessment of the capacity of dietary, endogenous and other agents to induce hormetic dose responses in oocytes, their supportive cells such as granulosa cells, blastocyst formation and early stage embryo development with the goal of improving fertility and reproductive success. The analysis showed that numerous agents enhance oocyte maturation and blastocyst/embryonic development in an hormetic fashion. These findings indicate that numerous agents improve oocyte-related biological functioning under normal conditions as well as enhancing its capacity to prevent damage from numerous chemical toxins and related stressor agents, including heat and age-related processes in pre-post conditioning and concurrent exposures. The present assessment suggests that hormetic-based lifestyles and dietary interventions may offer the potential to enhance healthy reproductive performance with applications to animal husbandry and human biology. The present findings also significantly extend the generality of the hormesis dose response concept to multiple fundamental biological processes (i.e., oocyte maturation, fertilization and blastocyst/embryo development)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
27. Investigating hormesis, aging, and neurodegeneration: From bench to clinics.
- Author
-
Calabrese V, Wenzel U, Piccoli T, Jacob UM, Nicolosi L, Fazzolari G, Failla G, Fritsch T, Osakabe N, and Calabrese EJ
- Abstract
Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology., Competing Interests: Conflict of interest: Vittorio Calabrese serves as Editor in Chief of Open Medicine, but it did not influenced peer-review process. Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)
- Published
- 2024
- Full Text
- View/download PDF
28. Muller and mutations: mouse study of George Snell (a postdoc of Muller) fails to confirm Muller's fruit fly findings, and Muller fails to cite Snell's findings.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Animals, Mice, History, 20th Century, Nobel Prize, X-Rays, Genetics history, Mutation
- Abstract
In 1931, Hermann J. Muller's postdoctoral student, George D. Snell (Nobel Prize recipient--1980) initiated research to replicate with mice Muller's X-ray-induced mutational findings with fruit flies. Snell failed to induce the two types of mutations of interest, based on fly data (sex-linked lethals/recessive visible mutations) even though the study was well designed, used large doses of X-rays, and was published in Genetics. These findings were never cited by Muller, and the Snell paper (Snell, Genetics 20:545-567, 1935) did not cite the 1927 Muller paper (Muller, Science 66:84, 1927). This situation raises questions concerning how Snell wrote the paper (e.g., ignoring the significance of not providing support for Muller's findings in a mammal). The question may be raised whether professional pressures were placed upon Snell to downplay the significance of his findings, which could have negatively impacted the career of Muller and the LNT theory. While Muller would receive worldwide attention, and receive the Nobel Prize in 1946 "for the discovery that mutations can be induced by X-rays," Snell's negative mutation data were almost entirely ignored by his contemporary and subsequent radiation genetics/mutation researchers. This raises questions concerning how the apparent lack of interest in Snell's negative findings helped Muller professionally, including his success in using his fruit fly data to influence hereditary and cancer risk assessment and to obtain the Nobel Prize., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
29. RUTIN, a widely consumed flavonoid, that commonly induces hormetic effects.
- Author
-
Calabrese EJ, Pressman P, Hayes AW, Dhawan G, Kapoor R, Agathokleous E, and Calabrese V
- Subjects
- Humans, Flavonoids pharmacology, Models, Biological, Vegetables, Hormesis, Rutin pharmacology
- Abstract
Rutin is a flavonoid present in numerous fruits and vegetables and therefore widely consumed by humans. It is also a popular dietary supplement of 250-500 mg/day. There is considerable consumer interest in rutin due to numerous reports in the biomedical literature of its multi-system chemo-preventive properties. The present paper provides the first assessment of rutin-induced hormetic concentration/dose responses, their quantitative features and mechanistic basis, along with their biological, biomedical, clinical, and public health implications. The findings indicate that rutin-induced hormetic dose responses are widespread, being reported in numerous biological models and cell types for a wide range of endpoints. Of critical importance is that the optimal hormetic findings shown in in vitro systems are currently not achievable for human populations due to low gastrointestinal tract bioavailability. These findings have the potential to strengthen future experimental studies with rutin, particularly concerning study design parameters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
30. Flavonoids commonly induce hormetic responses.
- Author
-
Calabrese EJ, Hayes AW, Pressman P, Dhawan G, Kapoor R, Agathokleous E, and Calabrese V
- Subjects
- Cell Survival, Dose-Response Relationship, Drug, Hormesis, Flavonoids toxicity
- Abstract
The present paper provides a new perspective of previously published findings by Siwak (Food Chem 141:1227-1241, 2013) which showed that 15 structurally diverse flavonoids reduced toxicity (i.e., enhanced cell viability) from hypochlorite using the MTT assay within a pre-conditioning experimental protocol, with each agent showing a similar biphasic concentration response relationship. We use this Commentary to point out that each of the concentration response relationships are consistent with the hormetic dose response. The paper of Siwak (Food Chem 141:1227-1241, 2013) is unique in that it provides a comparison of a relatively large number of agents using the identical experimental protocol., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
31. Taurine induces hormesis in multiple biological models: May have transformative implications for overall societal health.
- Author
-
Calabrese EJ, Pressman P, Hayes AW, Kapoor R, Dhawan G, Agathokleous E, and Calabrese V
- Subjects
- Hormesis, Models, Biological
- Abstract
This paper represents the first integrative assessment and documentation of taurine-induced hormetic effects in the biological and biomedical areas, their dose response features, mechanistic frameworks, and possible public health, therapeutic and commercial applications. Taurine-induced hormetic effects are documented in a wide range of experimental models, cell types and for numerous biological endpoints, with most of these experimental findings being reported within the past five years. It is suggested that the concept of hormesis may have a transformative effect on taurine research and its public health and therapeutic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
32. How Hermann J. Muller Viewed the Ernest Sternglass Contributions to Hereditary and Cancer Risk Assessment.
- Author
-
Calabrese EJ and Giordano J
- Subjects
- Humans, Child, Linear Models, Risk Assessment, Neoplasms
- Abstract
Abstract: As one of the most influential radiation geneticists of the 20th century, Hermann J. Muller had a major role in the development and widespread acceptance of the linear no-threshold (LNT) dose response for hereditary and cancer risk assessments worldwide. However, a spate of historical reassessments have challenged the fundamental scientific foundations of the LNT model, drawing considerable attention to issues of ethical probity and the scientific leadership of Muller. This review paper raises further questions about the objectivity of Muller with respect to the LNT model. It is shown that Muller supported Ernest Sternglass's findings and interpretations concerning radiation-induced childhood leukemia, which have been widely and consistently discredited. These findings provide further evidence that Muller's actions with respect to radiation cancer risk assessment were far more ideologically than scientifically based., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Health Physics Society.)
- Published
- 2024
- Full Text
- View/download PDF
33. Cancer risk assessment, its wretched history and what it means for public health.
- Author
-
Calabrese EJ
- Subjects
- Humans, Risk Assessment, Public Health, Neoplasms
- Published
- 2024
- Full Text
- View/download PDF
34. Blood-Labyrinth Barrier in Health and Diseases: Effect of Hormetic Nutrients.
- Author
-
Cosentino A, Agafonova A, Modafferi S, Trovato Salinaro A, Scuto M, Maiolino L, Fritsch T, Calabrese EJ, Lupo G, Anfuso CD, and Calabrese V
- Subjects
- Humans, Endothelial Cells, Cochlea, Pericytes, Ear, Inner, Hearing Loss
- Abstract
Significance: The stria vascularis, located in the inner ear, consists of three layers, one of which is the blood-labyrinth barrier (BLB). It is formed by endothelial cells, sealed together to prevent the passage of toxic substances from the blood to the inner ear, by pericytes and perivascular-resident macrophage-like melanocyte. Recent Advances: There are various causes that lead to hearing loss, and among these are noise-induced and autoimmune hearing loss, ear disorders related to ototoxic medication, Ménière's disease, and age-related hearing loss. For all of these, major therapeutic interventions include drug-loaded nanoparticles, via intratympanic or intracochlear delivery. Critical Issues: Since many pathologies associated with hearing loss are characterized by a weakening of the BLB, in this review, the molecular mechanisms underlying the response to damage of BLB cellular components have been discussed. In addition, insight into the role of hormetic nutrients against hearing loss pathology is proposed. Future Directions: BLB cellular components of neurovascular cochlear unit play important physiological roles, owing to their impermeable function against all ototoxic substances that can induce damage. Studies are needed to investigate the cross talk occurring between these cellular components to exploit their possible role as novel targets for therapeutic interventions that may unravel future path based on the use of hormetic nutrients. Antioxid. Redox Signal. 40, 542-563.
- Published
- 2024
- Full Text
- View/download PDF
35. Quercetin induces its chemoprotective effects via hormesis.
- Author
-
Calabrese EJ, Hayes AW, Pressman P, Dhawan G, Kapoor R, Agathokleous E, and Calabrese V
- Subjects
- Humans, Models, Biological, Dose-Response Relationship, Drug, Hormesis, Quercetin pharmacology
- Abstract
Quercetin is a polyphenol present in numerous fruits and vegetables and therefore widely consumed by humans with average daily dietary intakes of 10-20 mg/day. It is also a popular dietary supplement of 250-1000 mg/day. However, despite the widespread consumer interest in quercetin, due to its possible chemopreventive properties, the extensively studied quercetin presents a highly diverse and complex array of biological effects. Consequently, the present paper provides the first assessment of quercetin-induced hormetic concentration/dose responses, their quantitative features and mechanistic foundations, and their biological, biomedical, clinical, and public health implications. The findings indicate that quercetin-induced hormetic dose responses are widespread, being independent of biological model, cell type, and endpoint. These findings have the potential to enlighten future experimental studies with quercetin especially with respect to study design parameters and may also affect the appraisal of possible public health benefits and risks associated with highly diverse consumer consumption practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
36. Muller misled the Pugwash Conference on radiation risks.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Humans, Dose-Response Relationship, Radiation, Risk Assessment methods, Radiation, Ionizing, Nobel Prize
- Abstract
The Pugwash Conferences have been a highly visible attempt to create profoundly important discussions on matters related to global safety and security at the highest levels, starting in 1957 at the height of the Cold War. This paper assesses, for the first time, the formal comments offered at this first Pugwash Conference by the Nobel Prize-winning radiation geneticist, Hermann J. Muller, on the effects of ionizing radiation on the human genome. This analysis shows that the presentation by Muller was highly biased and contained scientific errors and misrepresentations of the scientific record that resulted in seriously misleading the attendees. The presentation of Muller at Pugwash served to promote, on a very visible global scale, continued misrepresentations of the state of the science and had a significant impact on policies and practices internationally and both scientific and personal belief systems concerning the effects of low dose radiation on human health. These misrepresentations would come to affect the adoption and use of nuclear technologies and the science of radiological and chemical carcinogen health risk assessment, ultimately having a profound effect on global environmental health.
- Published
- 2024
- Full Text
- View/download PDF
37. Evolution of hormesis research: a bibliometric analysis.
- Author
-
Agathokleous E and Calabrese EJ
- Subjects
- Hormesis, Bibliometrics
- Published
- 2024
- Full Text
- View/download PDF
38. Hormesis determines lifespan.
- Author
-
Calabrese EJ, Nascarella M, Pressman P, Hayes AW, Dhawan G, Kapoor R, Calabrese V, and Agathokleous E
- Subjects
- Animals, Humans, Aging physiology, Caenorhabditis elegans physiology, Stress, Physiological, Longevity physiology, Hormesis physiology
- Abstract
This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints (e.g., cell proliferation, memory, fecundity, growth, tissue repair, stem cell population expansion/differentiation, longevity). Evaluation of several hundred lifespan extending agents using yeast, nematode (Caenorhabditis elegans), multiple insect and other invertebrate and vertebrate models (e.g., fish, rodents), revealed they responded in a manner [average (mean/median) and maximum lifespans] consistent with the quantitative features [i.e., 30-60% greater at maximum (Hormesis Rule)] of the hormetic dose response. These lifespan extension features were independent of biological model, inducing agent, endpoints measured and mechanism. These findings indicate that hormesis describes the capacity to extend life via numerous agents and activities and that the magnitude of lifespan extension is modest, in the percentage, not fold, range. These findings have important implications for human aging, genetic diseases/environmental stresses and lifespan extension, as well as public health practices and long-term societal resource planning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
39. Muller's genetic load/species extinction hypothesis.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Humans, Animals, Mice, Rats, Swine, Genetic Load, Mutation, Radiation, Ionizing, Extinction, Biological, Radiation Exposure
- Abstract
The genetic load hypothesis of Hermann Muller raised the profound question of possible species extinction, even for humans, following a prolonged accumulation of recessive genes due to ionizing radiation exposure within the population. Two major mouse radiation research teams in the United States provided the most extensive tests of Muller's hypothesis. One group continued its study for more than two decades, over 82 consecutive generations, approximating 2500 human years. Even though Muller had stressed for decades his fear of species-threatening effects, no significant effects were observed for related factors such as reproductive fitness and longevity. Yet, the paper presenting the data of the 82-generation negative study has only been cited five times in 45 years. Altogether numerous laboratories worldwide collected vast amounts of data on mice, rats, and swine in an unsuccessful attempt to see if there was convincing evidence to support the genetic load theory and claims that species might deteriorate or be rendered extinct. This paper re-examines Muller's genetic load hypothesis with a new evaluation of how that hypothesis was tested and the significance of the findings, with most of those studies being completed before the BEIR I Committee Report in 1972. That committee briefly discussed the available evidence, mostly ignoring those results as they proceeded to make hereditary risk estimates both for (1) the first generation after a radiation exposure and (2) for the time, in the distant future, when a hypothetical genetic equilibrium would be reached. Their estimates assumed accumulation of harmful mutations and a linear no-threshold dose response extending all of the way down to a single ionization. More recent data on induction by ionizing radiation of dominant mutations that affect the skeletons of mice provide further robust supporting evidence that the generationally cumulative and LNT-based assumptions underpinning Muller's genetic load hypothesis are not correct., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
40. Comet assay and hormesis.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Dose-Response Relationship, Drug, Comet Assay, Research Design, Hormesis, DNA Damage
- Abstract
The paper provides the first assessment of the occurrence of hormetic dose responses using the Comet assay, a genotoxic assay. Using a priori evaluative criteria based on the Hormetic Database on peer-reviewed comet assay experimental findings, numerous examples of hormetic dose responses were obtained. These responses occurred in a large and diverse range of cell types and for agents from a broad range of chemical classes. Limited attempts were made to estimate the frequency of hormesis within comet assay experimental studies using a priori entry and evaluative criteria, with results suggesting a frequency in the 40% range. These findings are important as they show that a wide range of genotoxic chemicals display evidence that is strongly suggestive of hormetic dose responses. These findings have significant implications for study design issues, including the number of doses selected, dose range and spacing. Likewise, the widespread occurrence of hormetic dose responses in this genotoxic assay has important risk assessment implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
41. Environmental hormesis: New developments.
- Author
-
Agathokleous E, Calabrese EJ, and Barceló D
- Subjects
- Dose-Response Relationship, Drug, Hormesis
- Abstract
Competing Interests: Declaration of competing interest This project did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that there is no conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
42. Hermann Muller and his LNT scientific and policy leadership: Private communication reveals uncertainties.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Humans, Dose-Response Relationship, Radiation, Risk Assessment, Linear Models, Leadership, Neoplasms, Radiation-Induced
- Abstract
The present paper highlights numerous publications of Hermann J. Muller with a focus on his opinions concerning the validity of the linear no-threshold dose response model for hereditary and cancer risk assessment. These comments reflect a very consistent and powerfully supporting position for the LNT model. However, newly discovered correspondence between Muller and Robley D. Evans reveals that Muller was highly uncertain about the supportive science, and therefore hid his real opinions, deliberately misleading the scientific community and governmental agencies. Of further historical value is that in the correspondence with Evans, Muller proposed what might be the first articulation of an environmentally based Precautionary Principle. These perspectives have remained unknown since Muller requested Evans to keep this letter private., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
43. Background radiation and cancer risks: A major intellectual confrontation within the domain of radiation genetics with multiple converging biological disciplines.
- Author
-
Calabrese EJ and Selby PB
- Subjects
- Humans, Radiation Genetics, Radiation, Ionizing, Dose-Response Relationship, Radiation, Risk Assessment, Background Radiation, Neoplasms, Radiation-Induced epidemiology, Neoplasms, Radiation-Induced genetics
- Abstract
This paper assesses the judgments of leading radiation geneticists and cancer risk assessment scientists from the mid-1950s to mid-1970s that background radiation has a significant effect on human genetic disease and cancer incidence. This assumption was adopted by the National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel for genetic diseases and subsequently applied to cancer risk assessment by other leading individuals/advisory groups (e.g., International Commission on Radiation Protection-ICRP). These recommendations assumed that a sizeable proportion of human mutations originated from background radiation due to cumulative exposure over prolonged reproductive periods and the linear nature of the dose-response. This paper shows that the assumption that background radiation is a significant cause of spontaneous mutation, genetic diseases, and cancer incidence is not supported by experimental and epidemiological findings, and discredits erroneous risk assessments that improperly influenced the recommendations of national and international advisory committees, risk assessment policies, and beliefs worldwide.
- Published
- 2023
- Full Text
- View/download PDF
44. The challenges of defining hormesis in epidemiological studies: The case of radiation hormesis.
- Author
-
Iavicoli I, Fontana L, Santocono C, Guarino D, Laudiero M, and Calabrese EJ
- Subjects
- Humans, Dose-Response Relationship, Radiation, Hormesis, Epidemiologic Studies, Radiation, Ionizing, Occupational Exposure, Radiation Exposure adverse effects
- Abstract
In the current radiation protection system, preventive measures and occupational exposure limits for controlling occupational exposure to ionizing radiation are based on the linear no-threshold extrapolation model. However, currently an increasing body of evidence indicates that this paradigm predicts very poorly biological responses in the low-dose exposure region. In addition, several in vitro and in vivo studies demonstrated the presence of hormetic dose response curves correlated to ionizing radiation low exposure. In this regard, it is noteworthy that also the findings of different epidemiological studies, conducted in different categories of occupationally exposed workers (e.g., healthcare, nuclear industrial and aircrew workers), observed lower rates of mortality and/or morbidity from cancer and/or other diseases in exposed workers than in unexposed ones or in the general population, then suggesting the possible occurrence of hormesis. Nevertheless, these results should be considered with caution since the identification of hormetic response in epidemiological studies is rather challenging because of a number of major limitations. In this regard, some of the most remarkable shortcomings found in epidemiological studies performed in workers exposed to ionizing radiation are represented by lack or inadequate definition of exposure doses, use of surrogates of exposure, narrow dose ranges, lack of proper control groups and poor evaluation of confounding factors. Therefore, considering the valuable role and contribution that epidemiological studies might provide to the complex risk assessment and management process, there is a clear and urgent need to overcome the aforementioned limits in order to achieve an adequate, useful and more real-life risk assessment that should also include the key concept of hormesis. Thus, in the present conceptual article we also discuss and provide possible approaches to improve the capacity of epidemiological studies to identify/define the hormetic response and consequently improve the complex process of risk assessment of ionizing radiation at low exposure doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
45. Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.
- Author
-
Osakabe N, Modafferi S, Ontario ML, Rampulla F, Zimbone V, Migliore MR, Fritsch T, Abdelhameed AS, Maiolino L, Lupo G, Anfuso CD, Genovese E, Monzani D, Wenzel U, Calabrese EJ, Vabulas RM, and Calabrese V
- Subjects
- Humans, Polyphenols pharmacology, Polyphenols therapeutic use, Cochlea, Aging physiology, Neurobiology, Deafness
- Abstract
There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.
- Published
- 2023
- Full Text
- View/download PDF
46. Sublethal chemical stimulation of arthropod parasitoids and parasites of agricultural and environmental importance.
- Author
-
Agathokleous E, Blande JD, Masui N, Calabrese EJ, Zhang J, Sicard P, Guedes RNC, and Benelli G
- Abstract
An increasing number of studies have reported stimulation of various organisms in the presence of environmental contaminants. This has created a need to critically evaluate sublethal stimulation and hormetic responses of arthropod parasitoids and parasites following exposure to pesticides and other contaminants. Examining this phenomenon with a focus on arthropods of agricultural and environmental importance serves as the framework for this literature review. This review shows that several pesticides, with diverse chemical structures and different modes of action, applied individually or in combination at sublethal doses, commonly stimulate an array of arthropod parasitoids and parasites. Exposure at sublethal doses can enhance responses related to physiology (e.g., respiration, total lipid content, and total protein content), behavior (e.g., locomotor activity, antennal drumming frequency, host location, and parasitization), and fitness (longevity, growth, fecundity, population net and gross reproduction). Concordantly, the parasitic potential (e.g., infestation efficacy, parasitization rate, and parasitoid/parasite emergence) can be increased, and as a result host activities inhibited. There is some evidence illustrating hormetic dose-responses, but the relevant literature commonly included a limited number and range of doses, precluding a robust differentiation between sub- and superNOAEL (no-observed-adverse-effect level) stimulation. These results reveal a potentially significant threat to ecological health, through stimulation of harmful parasitic organisms by environmental contaminants, and highlight the need to include sublethal stimulation and hormetic responses in relevant ecological pesticide risk assessments. Curiously, considering a more utilitarian view, hormesis may also assist in optimizing mass rearing of biological control agents for field use, a possibility that also remains neglected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
47. How self-interest and deception led to the adoption of the linear non-threshold dose response (LNT) model for cancer risk assessment.
- Author
-
Selby PB and Calabrese EJ
- Abstract
This paper clarifies scientific contributions and deceptive/self-serving decisions of William L. Russell and Liane Russell that led to the adoption of the linear non-threshold (LNT) model for cancer risk assessment by the US EPA. By deliberately failing to report an extremely large cluster of mutations in the control group of their first experiment, and thereby greatly suppressing its mutation rate, the Russells incorrectly claimed that the male mouse was 15-fold more susceptible to ionizing-radiation-induced gene mutations as compared with fruit flies. This self-serving error not only propelled their research program into one of great prominence, but it also promoted the LNT-based doubling dose (DD) concept in radiation genetics/cancer risk assessment, by the US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel (1956). The DD concept became a central element in their recommendation that regulatory agencies switch from a threshold to an LNT model. This error occurred because of a decision by W. Russell not to report that a large cluster of control group mutations found in an experiment for which preliminary results were reported in 1951. This failure to report that cluster and similar clusters continued throughout the careers of the Russells, resulting in massive overestimation of low dose radiation risks supporting the LNT. The Russell database and the repeated claim that those data show that there is no threshold dose rate for mutation in irradiated mouse stem-cell spermatogonia, have provided mechanistic validation supporting the epidemiological LNT hypothesis for radiation-induced leukemias and cancers. This reanalysis supports the threshold model for both males and females, thereby rebutting epidemiological extrapolations from the NAS and EPA claiming support for the LNT hypothesis for cancer risk assessment. The implications of the Russell errors/deceptions, how/why they occurred, and their impact upon society are enormous and need to be addressed by scientific/regulatory agencies, affecting regulatory and litigation activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
48. Confirmation that Hermann Muller was dishonest in his Nobel Prize Lecture.
- Author
-
Calabrese EJ
- Subjects
- Male, Humans, Germ Cells, Linear Models, Radiation, Ionizing, Nobel Prize, Carcinogens
- Abstract
In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for ionizing radiation-induced germ cell mutations was linear and that there was ''no escape from the conclusion that there is no threshold''. However, a newly discovered commentary by the Robert L. Brent (2015) indicated that Curt Stern, after reading a draft of part of Muller's Nobel Prize Lecture, called Muller, strongly advising him to remove reference to the flawed linear non-threshold (LNT)-supportive Ray-Chaudhuri findings and strongly encouraged him to be guided by the threshold supportive data of Ernst Caspari. Brent indicated that Stern recounted this experience during a genetics class at the University of Rochester. Brent wrote that Muller refused to follow Stern's advice, thereby proclaiming support for the LNT dose-response while withholding evidence that was contrary during his Nobel Prize Lecture. This finding is of historical importance since Muller's Nobel Prize Lecture gained considerable international attention and was a turning point in the acceptance of the linearity model for radiation and chemical hereditary and carcinogen risk assessment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
49. Hormesis defines the limits of lifespan.
- Author
-
Calabrese EJ, Osakabe N, Di Paola R, Siracusa R, Fusco R, D'Amico R, Impellizzeri D, Cuzzocrea S, Fritsch T, Abdelhameed AS, Wenzel U, Franceschi C, and Calabrese V
- Subjects
- Humans, Aged, Aging physiology, Adaptation, Physiological, Antioxidants, Hormesis physiology, Longevity
- Abstract
This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
50. Stimulation of insect vectors of pathogens by sublethal environmental contaminants: A hidden threat to human and environmental health?
- Author
-
Agathokleous E, Blande JD, Calabrese EJ, Guedes RNC, and Benelli G
- Abstract
Sublethal stimulation and hormetic responses are increasingly identified and acknowledged in scientific research. However, the occurrence and characteristics of such responses in insect vectors of pathogens are little explored and poorly understood. Here, we collate significant evidence from the scientific literature showing that sublethal doses of environmental contaminants, such as pesticides, microplastics, and plasticizers, induce stimulation and hormetic responses in insect vectors of pathogens of agricultural and public health importance, including mosquitoes, other dipterans, psyllids, aphids, and planthoppers. Physiological, behavioral, and demographic traits can be enhanced by exposure to lower subtoxic contaminant doses while being inhibited by higher toxic doses. Energetic trade-offs can also occur, especially at sublethal doses higher than the no-observed-adverse-effect level (NOAEL). The relevant literature is limited and so are the number of doses commonly included in the studies, precluding firm conclusions and enhanced understanding. Nevertheless, these effects are significant and could undermine human and environmental health, and thus sustainability agendas, if ultimately the transmission of pathogens and disease spread and severity are increased. Further research is urgently needed to tackle these phenomena, especially under field conditions. The findings discussed here are relevant to chemical risk assessment and chemical safety evaluations, in which all possible effects from the lowest to higher doses should be considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.