Deuterium-depletedwater as adjuvant therapeutic agent for treatment of diet-induced obesity in rats

In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments. Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver. Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1β, IL-6, IFNγ) and anti-inflammatory TNFff were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome. In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFN) was observed. This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities. © 2019 by the author

Mitochondrial activity of cancer and normal mesenchymal stem cells in vitro cultured in medium with different deuterium content

We showed that cancer and normal mesenchymal stem/stromal (MSC) cells in vitro in a deuterated growth medium show a decrease of mitochondrial activity (MA), while in a deuterium-depleted medium an increase. This was established using mitotracker and rhodamine 123, and was also confirmed by expression of the UCP1 gene. The correlation dependence of mitochondrial activity in a medium with a changed ratio of deuterium/protium (D/H) and supramolecular structures was established, using the laser diffraction method. Density inhomogeneities in the deuterated medium are noted to be large, and in the deuterium-depleted medium small, in comparison with the control

Development of zinc-enriched medicinal and food plants

The decrease in the content of heavy isotopes of hydrogen (D) and oxygen (17O, 18O) in water is accompanied by a change in metabolic processes in plant and animal organisms, which is explained by the isotopic kinetic effect. This phenomenon underlies the technology of accumulation of microelements in medicinal and non-medicinal plants used for soft correction of hypoelementoses. The new technology includes isotope management of plant development; new laser methods for end-to-end quality control of aqueous solutions for irrigation and hydroponics of plants; a set of methods for end-to-end control of plant raw material enrichment in a microelement; online control of biotoxicity of plant raw materials and medicines made from them. Thus, in our work, the possibility of the development of metal-modified plants with zinc content of 1.4 mg/g dry basis is shown. © 2020 EManuscript Technologies. All rights reserved

D/H control of chemical kinetics in water solutions under low deuterium concentrations

Variations in the isotopic composition drastically changes properties of molecules. This also applies to H2O, one of the most indispensable substances on Earth. Here we investigated physical, chemical and biological characteristics of deuterium depleted water (0.5 mM HDO) compared to water with natural deuterium content (16 mM HDO) and heavy water D2O. Reaction systems of different organization levels were probed: molecular (galactose mutarotation), supramolecular (destabilase-lysozyme activity), two-phase heterogenic (suspension of slightly water-soluble active pharmaceutical ingredients), and living cells (unicellular biosensor S. ambigua lifespan). We have shown that the mutarotation rate constant for the L-galactose was 2-fold less than that for the D-isomer over the whole temperature range without dependence on HDO concentration in low values, whereas the first-order mutarotation kinetics was not observed for L-galactose in heavy water. Interestingly, the initial rate of lysozyme activity of destabilase-lysozyme increased two-fold in deuterium-depleted water whereas there was no activity change in heavy water. In suspension system, the dissolution kinetics of active pharmaceutical ingredients conformed with the normal kinetic isotope effect when kH/kD > 1. This confirms the important role of variations in the solvent (water) isotopic composition in the dissolution process acceleration. However, the most important isotope effect was observed in the living cells, where the rate constant for the processes of irreversible S. ambigua cell transition (from an active state to an immobilized state) increased up to 800 times under deuterium depletion. © 2018 Elsevier B.V

D/H control of chemical kinetics in water solutions under low deuterium concentrations

Variations in the isotopic composition drastically changes properties of molecules. This also applies to H2O, one of the most indispensable substances on Earth. Here we investigated physical, chemical and biological characteristics of deuterium depleted water (0.5 mM HDO) compared to water with natural deuterium content (16 mM HDO) and heavy water D2O. Reaction systems of different organization levels were probed: molecular (galactose mutarotation), supramolecular (destabilase-lysozyme activity), two-phase heterogenic (suspension of slightly water-soluble active pharmaceutical ingredients), and living cells (unicellular biosensor S. ambigua lifespan). We have shown that the mutarotation rate constant for the L-galactose was 2-fold less than that for the D-isomer over the whole temperature range without dependence on HDO concentration in low values, whereas the first-order mutarotation kinetics was not observed for L-galactose in heavy water. Interestingly, the initial rate of lysozyme activity of destabilase-lysozyme increased two-fold in deuterium-depleted water whereas there was no activity change in heavy water. In suspension system, the dissolution kinetics of active pharmaceutical ingredients conformed with the normal kinetic isotope effect when kH/kD > 1. This confirms the important role of variations in the solvent (water) isotopic composition in the dissolution process acceleration. However, the most important isotope effect was observed in the living cells, where the rate constant for the processes of irreversible S. ambigua cell transition (from an active state to an immobilized state) increased up to 800 times under deuterium depletion. © 2018 Elsevier B.V

In Vitro Study of Deuterium Effect on Biological Properties of Human Cultured Adipose-Derived Stem Cells

In current in vitro study we have shown the impact of deuterium content in growth medium on proliferation rate of human cultured adipose-derived stem cells (ADSC). ADSCs have also demonstrated morphological changes when cultured in deuterated growth medium: the cell cultures did not reach confluence but acquired polygonal morphology with pronounced stress fibers. At high deuterium concentrations the ADSCs population doubling time increased which indicated the cell cycle retardation and decrease of cell proliferation rate. The deuterated and deuterium-depleted growth media demonstrated acute and chronic cytotoxicity, respectively. The minimal migration ability was observed in deuterated medium whereas the highest migration activity was observed in the medium with the deuterium content close to natural. The cells in deuterated growth medium demonstrated decrease in metabolic activity after three days in culture. In contrast, in deuterium-depleted medium there was an increase in ADSC metabolic activity. © 2018 Alona Zlatska et al

Dependence of Biocatalysis on D/H Ratio: Possible Fundamental Differences for High-Level Biological Taxons

The kinetics of biological reactions depends on the deuterium/protium (D/H) ratio in water. In this work, we describe the kinetic model of biocatalytic reactions in living organisms depending on the D/H ratio. We show that a change in the lifetime or other characteristics of the vital activity of some organisms in response to a decrease or increase in the content of deuterium in the environment can be a sign of a difference in taxons. For animals—this is a curve with saturation according to the Gauss’s principle, for plants—it is the Poisson dependence, for bacteria a weakly saturated curve with a slight reaction to the deuterium/protium ratio toward increasing deuterium. The biological activity of the aquatic environment with reduced, elevated, and natural concentrations of deuterium is considered. The results of the study are presented in different vital indicators of some taxons: the bacteria kingdom—the colony forming units (CFU) index (Escherichia coli); animals—the activation energy of the death of ciliates (Spirostomum ambiguum), embryogenesis of fish (Brachydanio rerio); plants—germination and accumulation of trace elements Callisia fragrans L., sprouting of gametophores and peptidomics of moss Physcomitrella patens. It was found that many organisms change their metabolism and activity, responding to both high and low concentrations of deuterium in water. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

The Influence of Deuterium on the Properties of Pharmaceutical Substances (Review)

Introduction. The study discusses the hydrogen isotope 2H effect on the biological activity of pharmaceutical substances.Text. Two aspects of the deuterium effect on the properties of active pharmaceutical ingredients and excipients are considered. The first one involves the use of deuterated substances, new compounds or substituted counterparts. Replacing protium with deuterium is used to reduce the rate of biotransformation. The kinetic isotope effect (KIE), expressed in a decrease in the rate of biotransformation as a result of deuteration, allows us to predict the rapid development of new directions in the development of pharmaceuticals. With the same therapeutic effect, an improvement in pharmacokinetic characteristics, a decrease in toxicity, a blocking of the epimerization of optically active substances, a change in the mechanisms of action are observed. The second aspect of the deuterium effect is associated with an increase in KIE of known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) lower than in natural water. For the first time, dose-response diagrams for deuterium demonstrate identity with essential microelements. There is a safety zone for the certain D/H relationship, beyond which the organism's vitality decreases. Improved kinetic characteristics are demonstrated for molecular level and for biological objects of various hierarchical levels. In particular, they include the possibility of increasing the dissolution rate of substances, the influence on the processes of mutarotation and the optical activity of chiral substances, the degree of accumulation of necessary elements in medicinal plants, and other processes.Conclusion. The results make it possible to predict the mechanisms of deuterium influence on the biochemical transformations of pharmaceutical substances in the body