Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations

Calabrese, Edward J.

doi:10.1016/j.phrs.2015.12.021

Cited by 187 publications

(109 citation statements)

References 261 publications

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“…The phenomenon of low dose stimulation, with simultaneous high-dose inhibition response, is known as hormetic dose response (Calabrese and Blain 2009). Calabrese (2014, 2016) has assessed that the frequency of hormetic dose response in toxicological studies does not exceed 37%. Therefore, our Cd-tolerant lines, in which hormesis occurs, can be used as a model system to study this feature, classified as the first quantitative description of biological plasticity (Calabrese 2014).…”

Section: Resultsmentioning

confidence: 99%

Comparative Assessment of Response to Cadmium in Heavy Metal-Tolerant Shrubs Cultured In Vitro

Wiszniewska

Hanus-Fajerska

Muszyńska

et al. 2017

Water Air Soil Pollut

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Two species of Pb-adapted shrubs, Alyssum montanum and Daphne jasminea, were evaluated in vitro for their tolerance to elevated concentrations of cadmium. Shoot cultures were treated with 0.5, 2.5, and 5.0 μM CdCl2 for 16 weeks and analyzed for their organogenic response, biomass accretion, pigment content, and macronutrient status. Cadmium accumulation and its root-to-shoot translocation were also determined. In both species, rooted microplantlets, suitable for acclimatization, were obtained in the presence of Cd applied as selection agent. In A. montanum, low and moderate dose of Cd stimulated multiplication, rooting, and biomass production. Growth tolerance index (GTI) in Cd-treated shoots ranged from 120 to 215%, while in the roots 51–202%. In turn, in Cd-treated D. jasminea proliferation and rooting were inhibited, and GTI for shoots decreased with increasing doses of Cd. However, roots exposed to Cd had higher biomass accretion. Both species accumulated Cd in developed organs, and its content increased with increasing CdCl2 dose. Interestingly, D. jasminea accumulated higher amounts of Cd in the roots than A. montanum and immobilized this metal in the root system. On the contrary, A. montanum translocated some part of accumulated Cd to the shoots, but with low efficiency. In the presence of Cd, A. montanum maintained macronutrient homeostasis and synthesized higher amounts of phytosynthetic pigments in the shoots. D. jasminea accumulated root biomass, immobilized Cd, and restricted its translocation at the expense of nutrient balance. Considering remediation potential, A. montanum could be exploited in phytoextraction, while D. jasminea in phytostabilization of polluted substrate.

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Section: Resultsmentioning

confidence: 99%

Comparative Assessment of Response to Cadmium in Heavy Metal-Tolerant Shrubs Cultured In Vitro

Wiszniewska

Hanus-Fajerska

Muszyńska

et al. 2017

Water Air Soil Pollut

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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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“…This phenomenon, generally referred to as ‘hormesis’, is strongly conserved in evolution and can be induced by many and varied perturbations including (among others) oxidative stress, ER stress, inflammatory stimuli, and temperature shift, all of which disrupt cellular proteostasis (Rutkowski et al, 2006; Calabrese, 2014; Mollereau et al, 2014; Rzechorzek et al, 2015). Of note, a recent review compiled the effect of 154 distinct conditioning agents used in preconditioning or postconditioning experiments (Calabrese, 2016). In the last few years an increasing number of studies have focused on the importance of hormesis in pathologies such as neurodegenerative disease, cancer, diabetes and aging (Hetz and Mollereau, 2014; Martins et al, 2011; Mollereau, 2013; Mollereau et al, 2014; Perri et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Adaptive preconditioning in neurological diseases – therapeutic insights from proteostatic perturbations

et al. 2016

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In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a ‘proteostasis network’ and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge – the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson’s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses and the molecular pathways they recruit might be exploited for therapeutic gain.

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Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations

Cited by 187 publications

References 261 publications

Comparative Assessment of Response to Cadmium in Heavy Metal-Tolerant Shrubs Cultured In Vitro

Comparative Assessment of Response to Cadmium in Heavy Metal-Tolerant Shrubs Cultured In Vitro

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

Adaptive preconditioning in neurological diseases – therapeutic insights from proteostatic perturbations

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