HORMESIS: A Fundamental Concept with Widespread Biological and Biomedical Applications

Calabrese, Edward J.; Dhawan, Gaurav; Kapoor, Rachna; Iavicoli, Ivo; Calabrese, Vittorio

doi:10.1159/000441520

Cited by 67 publications

(37 citation statements)

References 49 publications

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“…For example, dose-response projections based on injury at moderate intensity would ignore if lower intensities might in fact provide protection from injury (i.e. so called hormetic dose response; [182], [183]). Especially in the absence of a mechanistic explanation for damage supporting a particular dose-response curve, and accumulation of data from different model systems and varying lesion measures we avoided extrapolation beyond tested stimulation intensities.…”

Section: Assumptions Regarding Dose-response Curves For Safety Data Fmentioning

confidence: 99%

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

et al. 2016

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This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

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Section: Assumptions Regarding Dose-response Curves For Safety Data Fmentioning

confidence: 99%

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

et al. 2016

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“…). Hence, cellular hormesis defines a general phenomenon in which a mild stress‐induced stimulation results in biologically beneficial effects (Calabrese et al, b) (Fig. ).…”

Section: Brain Response In Vad: a Role For Hormetic Effects And Precomentioning

confidence: 99%

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Calabrese

Giordano

Signorile

et al. 2016

J of Neuroscience Research

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129

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Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally associated with neurovascular degeneration, in which neuronal damage and blood-brain barrier alterations coexist and evoke beta-amyloid-induced oxidative and nitrosative stress, mitochondrial dysfunction, and inflammasome- promoted neuroinflammation, which contribute to and exacerbate the course of disease. Vascular cognitive impairment comprises a heterogeneous group of cognitive disorders of various severity and types that share a presumed vascular etiology. The present study reviews major pathogenic factors involved in VaD, highlighting the relevance of cerebrocellular stress and hormetic responses to neurovascular insult, and addresses these mechanisms as potentially viable and valuable as foci of novel neuroprotective methods to mitigate or prevent VaD. © 2016 Wiley Periodicals, Inc.

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“…Firstly UBI is clearly an example of the well-known phenomenon called “hormesis” or “biphasic dose response’. This phenomenon has been well reviewed by Edward Calabrese from U Mass Amherst [73, 74]. The basic concept states that any toxic chemical substance or drug, or any physical insult (such as ionizing radiation, hyperthermia, or oxidative stress) can be beneficial, protective or even therapeutic, provided the dose is low enough.…”

Section: Mechanisms Of Action Of Ubimentioning

confidence: 99%

Ultraviolet Irradiation of Blood: “The Cure That Time Forgot”?

Hamblin

2017

Advances in Experimental Medicine and Biology

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Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called “the cure that time forgot”. Later studies were mostly performed by Russian workers and in other Eastern countries and the modern view in Western countries is that UBI remains highly controversial. This chapter discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. No resistance of microorganisms to UV irradiation has been reported, and multi- antibiotic resistant strains are as susceptible as their wild-type counterparts. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the blood-stream, as only 5–7% of blood volume needs to be treated with UV to produce the optimum benefit. UBI may enhance the phagocytic capacity of various phagocytic cells (neutrophils and dendritic cells), inhibit lymphocytes, and oxidize blood lipids. The oxidative nature of UBI may have mechanisms in common with ozone therapy and other oxygen therapies. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.

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HORMESIS: A Fundamental Concept with Widespread Biological and Biomedical Applications

Cited by 67 publications

References 49 publications

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Ultraviolet Irradiation of Blood: “The Cure That Time Forgot”?

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