scholarly journals Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 293
Author(s):  
Volker Schirrmacher
Keyword(s):  
Dose Response ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Oncolytic Viruses ◽  
Cellular Growth ◽  
Heat Radiation ◽  
Stress Adaptation ◽  
High Dose ◽  
Micro Rnas

A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness. Physical stress can be exerted through heat, radiation, or physical exercise. Chemical stressors include reactive species from oxygen (ROS), nitrogen (RNS), and carbon (RCS), carcinogens, elements, such as lithium (Li) and silicon (Si), and metals, such as silver (Ag), cadmium (Cd), and lead (Pb). Anthropogenic chemicals are agrochemicals (phytotoxins, herbicides), industrial chemicals, and pharmaceuticals. Biochemical stress can be exerted through toxins, medical drugs (e.g., cytostatics, psychopharmaceuticals, non-steroidal inhibitors of inflammation), and through fasting (dietary restriction). Key-lock interactions between enzymes and substrates, antigens and antibodies, antigen-presenting cells, and cognate T cells are the basics of biology, biochemistry, and immunology. Their rules do not obey linear dose-response relationships. The review provides examples of biologic stressors: oncolytic viruses (e.g., immuno-virotherapy of cancer) and hormones (e.g., melatonin, stress hormones). Molecular mechanisms of cellular stress adaptation involve the protein quality control system (PQS) and homeostasis of proteasome, endoplasmic reticulum, and mitochondria. Important components are transcription factors (e.g., Nrf2), micro-RNAs, heat shock proteins, ionic calcium, and enzymes (e.g., glutathion redox enzymes, DNA methyltransferases, and DNA repair enzymes). Cellular growth control, intercellular communication, and resistance to stress from microbial infections involve growth factors, cytokines, chemokines, interferons, and their respective receptors. The effects of hormesis during evolution are multifarious: cell protection and survival, evolutionary flexibility, and epigenetic memory. According to the hormesis theory, this is true for the entire biosphere, e.g., archaia, bacteria, fungi, plants, and the animal kingdoms.

scholarly journals Low Dose Ionising Radiation-Induced Hormesis: Therapeutic Implications to Human Health

2021 ◽  
Vol 11 (19) ◽  
pp. 8909
Author(s):  
Yeh Siang Lau ◽  
Ming Tsuey Chew ◽  
Amal Alqahtani ◽  
Bleddyn Jones ◽  
Mark A. Hill ◽  
...  
Keyword(s):  
Human Health ◽  
Dose Response ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Ionising Radiation ◽  
High Dose ◽  
Therapeutic Implications ◽  
Therapeutic Benefits ◽  
Biological Phenomena ◽  
Radiation Induced

The concept of radiation-induced hormesis, whereby a low dose is beneficial and a high dose is detrimental, has been gaining attention in the fields of molecular biology, environmental toxicology and radiation biology. There is a growing body of literature that recognises the importance of hormetic dose response not only in the radiation field, but also with molecular agents. However, there is continuing debate on the magnitude and mechanism of radiation hormetic dose response, which could make further contributions, as a research tool, to science and perhaps eventually to public health due to potential therapeutic benefits for society. The biological phenomena of low dose ionising radiation (LDIR) includes bystander effects, adaptive response, hypersensitivity, radioresistance and genomic instability. In this review, the beneficial and the detrimental effects of LDIR-induced hormesis are explored, together with an overview of its underlying cellular and molecular mechanisms that may potentially provide an insight to the therapeutic implications to human health in the future.

The marginalization of hormesis

2000 ◽  
Vol 19 (1) ◽  
pp. 32-40 ◽  
Author(s):  
E J Calabrese ◽  
L A Baldwin
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Close Association ◽  
Modern Medicine ◽  
High Dose ◽  
Multiple Factors ◽  
Toxicological Data ◽  
Dose Effects ◽  
Guilt By Association ◽  
Carry Over

Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades ofthe 20th century. These factors include: (a) the close-association of hormesis with homeopathy lead to the hostility of modern medicine toward homeopathy thereby creating a guilt by association framework, and the carry-over influence of that hostility in the judgements of medically-based pharmacologists/ toxicologists toward hormesis; (b) the emphasis of high dose effects linked with a lack of appreciation of the significance of the implications of low dose stimulatory effects; (c) the lack of an evolutionary-based mechanism(s) to account for hormetic effects; and (d) the lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective.

scholarly journals Carcinogenesis induced by low-dose radiation

2017 ◽  
Vol 51 (4) ◽  
pp. 369-377 ◽  
Author(s):  
Igor Piotrowski ◽  
Katarzyna Kulcenty ◽  
Wiktoria Maria Suchorska ◽  
Agnieszka Skrobała ◽  
Małgorzata Skórska ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Atomic Bomb ◽  
Threshold Model ◽  
Occupational Exposures ◽  
High Dose ◽  
Low Dose Radiation ◽  
Oncologic Patients ◽  
Risk Of Cancer ◽  
Dose Radiation

AbstractBackgroundAlthough the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.ConclusionsUnderstanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.

scholarly journals Testing the standardized growth curve (SGC) to OSL dating coastal sediments from the south Bohai Sea, China

2013 ◽  
Vol 40 (2) ◽  
pp. 101-112 ◽  
Author(s):  
Guang-Quan Chen ◽  
Liang Yi ◽  
Xing-Yong Xu ◽  
Hong-Jun Yu ◽  
Jian-Rong Cao ◽  
...  
Keyword(s):  
Growth Curve ◽  
Dose Response ◽  
Bohai Sea ◽  
Low Dose ◽  
Osl Dating ◽  
Coastal Sediments ◽  
High Dose ◽  
Coarse Silt ◽  
The South ◽  
Response Curves

AbstractIt has been suggested that the standardized growth curve (SGC) method can be used to accurately determinate equivalent dose (De) and reduce measurement time. However, different opinions regarding the applicability of the SGC method exist. In this paper, we evaluated quartz OSL SGCs of marine and coastal sediments of different grain sizes and different cores in the south Bohai Sea in China, and tested their applicability to the determination of De values. Our results suggested as follows: (1) The SGC method is applicable to both multiple- and single-aliquot regenerative-dose (MAR and SAR) protocols of OSL dating and efficiently provides reliable estimates of De. (2) Finesand quartz of different palaeodoses showed highly similar dose-response curves and an SGC was developed, but old samples using the SGC method have large uncertainties. (3) For coarse-silt quartz, two different types of dose-response curves were recorded: low-dose (≤60Gy) and high-dose (≥100Gy). The growth curves of low-dose quartz were similar to each other, facilitating the use of SGC in De estimations, but errors tended to be larger than those obtained in the SAR method. For high-dose (100–300Gy) quartz, the SGC was also found to be reliable, but there was large uncertainty in De (>300Gy) estimation. We suggest that SGC could be employed for the dating of marine and coastal sediments dating using either MAR or SAR OSL protocol and either fine-silt, coarse-silt or fine-sand quartz.

scholarly journals Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness

2016 ◽  
Vol 57 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Eva Yi Kong ◽  
Shuk Han Cheng ◽  
Kwan Ngok Yu
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
High Dose ◽  
X Rays ◽  
Acridine Orange Staining ◽  
Living Organisms ◽  
Dose Responses ◽  
Different Levels ◽  
Danio Rerio Embryos

Abstract The in vivo low-dose responses of zebrafish ( Danio rerio ) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead.

scholarly journals Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats

2021 ◽  
Author(s):  
Ana CR Ribeiro ◽  
Elisa H Hawkins ◽  
Fay M Jahr ◽  
Joseph L McClay ◽  
Laxmikant S Deshpande
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Forced Swim Test ◽  
Preference Test ◽  
Complete Recovery ◽  
Male Rats ◽  
High Dose ◽  
Adult Rats ◽  
Dose Dependent

Organophosphate (OP) chemicals include commonly used pesticides and also chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. While a chronic low-dose OP exposure does not produce acute cholinergic crises, epidemiological studies report long-term neuropsychiatric issues including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of a single, high-dose CPF or studied sub-chronic behavioral effects particularly the motor and cognitive effects of repeated low-dose CPF exposure. However, studies on chronic mood and depression-related morbidities following repeated sub-threshold CPF doses that would mimic occupationally-relevant OP exposures are lacking. Here, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21-days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following an 11-week washout period, CPF-treated rats exhibited a dose-dependent increase in signs of anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) despite a complete recovery of ChE activity at this stage. We speculate that both cholinergic and non-cholinergic mechanisms could play a role in the development of chronic OP-related depressive outcomes. The proposed CPF exposure paradigm could provide an ideal model to further study molecular mechanisms underlying cause and effect relationships between environmental OP exposures and the development of chronic behavioral deficits.

Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.

1988 ◽  
Vol 6 (5) ◽  
pp. 762-768 ◽  
Author(s):  
D Thiébaud ◽  
P Jaeger ◽  
A F Jacquet ◽  
P Burckhardt
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Optimal Dose ◽  
Urinary Calcium ◽  
Plasma Calcium ◽  
High Dose ◽  
Initial Plasma ◽  
Plasma Calcium Concentration ◽  
Dose Dependent Decrease

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.

Hormesis, resveratrol and plant-derived polyphenols: some comments

2011 ◽  
Vol 30 (12) ◽  
pp. 2027-2030 ◽  
Author(s):  
Salvatore Chirumbolo
Keyword(s):  
Risk Assessment ◽  
Dose Response ◽  
Adaptive Response ◽  
Low Dose ◽  
High Dose ◽  
Low Doses ◽  
General Behaviour

Hormesis is a dose–response phenomenon, usually present in plants and animals, characterized by a low-dose stimulation and high-dose inhibition, often resulting in typical U-shaped or J-shaped curves. Hormesis has become an interesting model for toxicology and risk assessment, as it has been described for several nature-derived phytochemicals but also because this adaptive response to stressors might hide an underlying more general behaviour of cell towards low doses.

scholarly journals A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

2021 ◽  
Vol 22 (15) ◽  
pp. 7957
Author(s):  
Mihaela Tudor ◽  
Antoine Gilbert ◽  
Charlotte Lepleux ◽  
Mihaela Temelie ◽  
Sonia Hem ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Stress Responses ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Stress Granules ◽  
Cellular Mechanisms ◽  
Bystander Effects ◽  
Proteomic Study ◽  
Radiation Induced

Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules.

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