scholarly journals Possible Mechanisms of Biological Effects Observed in Living Systems during 2H/1H Isotope Fractionation and Deuterium Interactions with Other Biogenic Isotopes

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4101 ◽  
Author(s):  
Alexander Basov ◽  
Liliya Fedulova ◽  
Ekaterina Vasilevskaya ◽  
Stepan Dzhimak
Keyword(s):  
Metabolic Pathways ◽  
Intercellular Space ◽  
Isotope Fractionation ◽  
Biological Effects ◽  
Experimental Studies ◽  
Living Systems ◽  
Chemical Bonds ◽  
Molecular Effects ◽  
Tunnel Effects ◽  
New Hypothesis

This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable 2H/1H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with 18O/17O/16O, 15N/14N, 13C/12C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The comparative analysis of some experimental studies results revealed the following observation: “Isotopic shock” is highly probable and is observed mostly when chemical bonds form between atoms with a summary odd number of neutrons (i.e., bonds with a non-compensated neutron, which correspond to the following equation: Nn − Np = 2k + 1, where k ϵ Z, k is the integer, Z is the set of non-negative integers, Nn is number of neutrons, and Np is number of protons of each individual atom, or in pair of isotopes with a chemical bond). Data on the efficacy and metabolic pathways of the therapy also considered 2H-modified drinking and diet for some diseases, such as Alzheimer’s disease, Friedreich’s ataxia, mitochondrial disorders, diabetes, cerebral hypoxia, Parkinson’s disease, and brain cancer.

scholarly journals Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners

2021 ◽  
Vol 22 (15) ◽  
pp. 7885
Author(s):  
Vladimír Křen
Keyword(s):  
Neurological Diseases ◽  
Biological Effects ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Biological Targets ◽  
Molecular Effects ◽  
Anisotropic Systems ◽  
Specific Activities ◽  
Optically Pure

This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the “lock-and-key” concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of “silymarin applications” lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.

Ca isotope fractionation upon synthesis of carbonated apatite

2021 ◽  
Author(s):  
Michael E. Böttcher ◽  
Nikolaus Gussone ◽  
Anika C. Conrad ◽  
Iris Schmiedinger ◽  
Jens Fiebig ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Isotope Fractionation ◽  
Solid Phase ◽  
Experimental Studies ◽  
Apatite Formation ◽  
Calcium Isotope ◽  
Hydroxy Apatite ◽  
Carbonated Apatite ◽  
Batch Type ◽  
Synthetic Calcite

<p>Carbonated hydroxy-apatite (CHAP) was experimentally synthesized in batch-type set-ups by mixing of calcium (Ca)- and phosphate-bearing aqueous solutions and the transformation of calcite powder in aqueous solution between 11° and 65°C (Gussone et al., 2020). Compositional changes of the experimental solution and solid phase products were followed by elemental analysis, Raman spectroscopy, scanning-electron microscopy, and powder XRD. In the mixing experiments, crystallization of CHAP took place following the precipitation of metastable brushite as precursor that was then transformed into CHAP. In the transformation experiments using synthetic calcite as a precursor phase it was found that the reaction at pH values between 7.5 and 7.9 occurs via the direct replacement of calcium carbonate by CHAP.</p><p>Calcium isotope fractionation led to an enrichment of the light isotope in the solid CHAP compared to the aqueous solution by about -0.5 to -1.1 ‰, independent from the experimental approach, and the magnitude was essentially independent of temperature. The metastable brushite formed prior to transformation to CHAP showed a reduced fractionation compared to the CHAP. The observed Ca isotope fractionation into the CHAP lattice resembles that of natural phosphorites and lies within the range of the view existing theoretical and experimental studies.</p><p> </p><p>Reference: Gussone N., Böttcher M.E., Conrad A.C., Fiebig J., Pelz M., Grathoff G., Schmidt B.C. (2020) Calcium isotope fractionation upon experimental apatite formation. Chem. Geol., 551, 119737</p><p>The study was supported by German Science Foundation (DFG) to M.E.B and J.F. within the EXCALIBOR project (BO1548/8 and FI 948/7), and to N.G. (GU1035/10), and by Leibniz IOW.</p>

MECHANISMS OF FRACTIONATION OF STABLE ISOTOPES IN LIVING SYSTEMS

2021 ◽  
Author(s):  
Stepan S. Dzhimak ◽  
◽  
Anna Elkina ◽  
Alexandr A. Basov ◽  
◽  
...  
Keyword(s):  
Stable Isotopes ◽  
Exchange Interaction ◽  
Intercellular Space ◽  
Living Systems ◽  
Complete Understanding ◽  
Integer Spin ◽  
Half Integer ◽  
Physical Laws

Some physical laws are considered that provide stable fractionation of isotopes, leading to the accumulation of certain isotopic forms in the intracellular and intercellular space with the manifestation of these effects at various levels of the organism. It is suggested that for a more complete understanding of the above processes, it is necessary to study the mechanism of exchange interaction between particles with integer spin (bosons) and half-integer spin (fermions).

scholarly journals In Silico Investigation of Mitragynine and 7-Hydroxymitragynine Metabolism

2019 ◽  
Author(s):  
Taweetham Limpanuparb ◽  
Rattha Noorat ◽  
Yuthana Tantirungrotechai
Keyword(s):  
Gas Phase ◽  
In Silico ◽  
Metabolic Pathways ◽  
Experimental Studies ◽  
Medicinal Uses ◽  
Detection Techniques ◽  
Mass Spectrom ◽  
Gibbs Energies ◽  
In Silico Study

Abstract Objective: Mitragynine is the main active compound of Mitragyna speciose (Kratom in Thai). The understanding of mitragynine derivative metabolism in human body is required to develop effective detection techniques in case of drug abuse or establish an appropriate dosage in case of medicinal uses. This in silico study is based upon in vivo results in rat and human by Philipp et al. (J. Mass Spectrom., 2009, 44, 1249.) Results: The gas-phase structures of mitragynine, 7-hydroxymitragynine and their metabolites were obtained by quantum chemical method at B3LYP/6-311++G(d,p) level. Results in terms of standard Gibbs energies of reaction for all metabolic pathways are reported with solvation energy from SMD model. We found that 7-hydroxy substitution leads to changes in reactivity in comparison to mitragynine: position 17 is more reactive towards demethylation and conjugation to a glucuronide and position 9 is less reactive towards conjugation to a glucuronide. Despite the changes, position 9 is the most reactive for demethylation and position 17 is the most reactive for conjugation to a glucuronide for both mitragynine and 7-hydroxymitragynine. Our results suggest that 7-hydroxy substitution could lead to different metabolic pathways and raise an important question for further experimental studies of this more potent derivative.

scholarly journals EVALUATION OF TOXIC EFFECTS OF MAGNETIC CONTRAST DIAGNOSTIC GADOLINIUM-CONTAINING NANOCOMPOSITE

2019 ◽  
Vol 98 (10) ◽  
pp. 1161-1165
Author(s):  
Larisa M. Sosedova ◽  
E. A. Titov ◽  
M. A. Novikov ◽  
V. A. Vokina ◽  
V. S. Rukavishnikov
Keyword(s):  
Nervous Tissue ◽  
Chemical Elements ◽  
Biological Effects ◽  
Experimental Studies ◽  
Biological Response ◽  
Immunohistochemical Method ◽  
Ether Anesthesia ◽  
Compensatory Response ◽  
White Rats ◽  
Liver And Kidney

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs. Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats. Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level. Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process. Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

2021 ◽  
Vol 29 (5) ◽  
pp. 25-33
Author(s):  
Vadzim Michailovich Vasilkevich ◽  
Ruslan Valerievich Bogdanov ◽  
Ksenia Sergeevna Gilevskaya ◽  
Victoria Igorevna Kulikouskaya
Keyword(s):  
Biological Effects ◽  
Experimental Studies ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Pectin Content ◽  
Target Organs ◽  
Toxicological Studies ◽  
Threshold Doses ◽  
20 Nm ◽  
Dose Dependent

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields. Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20-30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed. Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase. Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

scholarly journals Uric acid and inflammation in kidney disease

2020 ◽  
Vol 318 (6) ◽  
pp. F1327-F1340 ◽  
Author(s):  
Su Woong Jung ◽  
Su-Mi Kim ◽  
Yang Gyun Kim ◽  
Sang-Ho Lee ◽  
Ju-Young Moon
Keyword(s):  
Uric Acid ◽  
Immune System ◽  
Kidney Disease ◽  
Biological Effects ◽  
Experimental Studies ◽  
Epidemiologic Studies ◽  
Causative Role ◽  
Immune System Activation ◽  
Progression Of Kidney Disease ◽  
System Activation

Asymptomatic hyperuricemia is frequently observed in patients with kidney disease. Although a substantial number of epidemiologic studies have suggested that an elevated uric acid level plays a causative role in the development and progression of kidney disease, whether hyperuricemia is simply a result of decreased renal excretion of uric acid or is a contributor to kidney disease remains a matter of debate. Over the last two decades, multiple experimental studies have expanded the knowledge of the biological effects of uric acid beyond its role in gout. In particular, uric acid induces immune system activation and alters the characteristics of resident kidney cells, such as tubular epithelial cells, endothelial cells, and vascular smooth muscle cells, toward a proinflammatory and profibrotic state. These findings have led to an increased awareness of uric acid as a potential and modifiable risk factor in kidney disease. Here, we discuss the effects of uric acid on the immune system and subsequently review the effects of uric acid on the kidneys mainly in the context of inflammation.

scholarly journals Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1792 ◽  
Author(s):  
Asma Ahmed AlGhamdi ◽  
Mohammed Razeeth Shait Mohammed ◽  
Mazin A. Zamzami ◽  
Abdulrahman L. Al-Malki ◽  
Mohamad Hasan Qari ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Nigella Sativa ◽  
Experimental Studies ◽  
Nucleotide Metabolism ◽  
Untargeted Metabolomics ◽  
Sphingolipid Metabolism ◽  
Cancer Cell Survival

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

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