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Biomedical subjects

E B Burlakova

Publications and source records attributed to E B Burlakova.

At least 19 recordsLinked to original sources

[Age-related peculiarities of effect of low dose ionizing radiation on blood antioxidant enzyme system status in Chernobyl's accident liquidation participant].

Age-dependency of activity of key blood antioxidant enzymes--superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase has been estimated in 104 men and women aged 25-60 years participated in the liquidation of the Chernobyl's accident since 6 years after irradiation. Control group includes 35 age-matched men and women. The results of study on 18 children aged 7-15 years and 5 children aged 2-6 years born by irradiated parents are given as well. Nineteen children were in the control group. Low-dose irradiation was found modify the pattern of age-related dependency of all enzymes studied. Most susceptible chain was enzymes of glutathione cycle both in liquidators and children. Study of late effects has shown that young people (<30 years) as well as children are most susceptible to low-level irradiation whereas most resistant were middle-aged people. This observation should be taken into consideration at selection of high-risk groups in an industry linked with chronic low-dose irradiation.

Adolescent↗

Pharmacological activity of phenazepam and flunitrazepam in ultralow doses.

Experiments on male outbred albino rats showed that benzodiazepine tranquilizers phenazepam and flunitrazepam in ultralow doses (10(-9)-10(-15) mol/kg) produced an anxiolytic effect in the conflict situation test. This effect was not accompanied by myorelaxing and sedative side effects typical of standard doses of tranquilizers.

Animals↗

Phenazepam in therapeutic and ultralow doses in vitro modulates the content of lipid peroxidation products and acetylcholinesterase activity in membrane fraction from mouse brain.

In vitro incorporation of tranquilizer phenazepam in a concentration of 10(-13) M into membrane fraction from mouse brain produced a prooxidant effect. In concentrations of 10(-5)-10(-9) and 10(-15)-10(-17) M this agent possessed antioxidant activity. Phenazepam significantly decreased the maximum rate of enzymatic reactions (10(-5) and 10(-15) M) and Michaelis constant (10(-5) M) for acetylcholinesterase. Incorporation of phenazepam in ultralow doses into membrane modified its lipid components (estimated by lipid peroxidation) and functional state, and this effect was comparable with the influence of this substance in standard doses. This probably contributes to the physiological effect of ultralow doses of phenazepam in.

Acetylcholinesterase↗

Inhibition of tumor growth with ultralow doses of doxorubicin under experimental conditions.

Antitumor activity of ultralow doses of cytostatic doxorubicin was studied on BDF1 mice with Lewis lung carcinoma. The preparation was injected intraperitoneally in single doses of 10(-5), 10(-10), 10(-15), and 10(-20) M on the next day after tumor inoculation. The effect of ultralow doses was compared with that of a standard therapeutic dose of doxorubicin (8 mg/kg, 1.4 x 10(-3) M). Doxorubicin in ultralow doses produced an antitumor effect comparable with that induced by the preparation in standard doses. On day 12 after administration of doxorubicin in ultralow and standard doses, tumor size in mice did not exceed 20% of the control level.

Animals↗

Effects of phenazepam in ultralow doses on bioelectric activity of the brain and behavior of rats in various models of anxiety.

Phenazepam in ultralow doses produced an anxiolytic effect on male outbred albino rats in the conflict situation and elevated plus-maze models and inhibited theta-activity in EEG, which is typical of tranquilizers. As differentiated from standard doses, phenazepam in this concentration did not affect other frequency bands. Our results suggest that phenazepam in ultralow doses acts as the anxioselective tranquilizer.

Animals↗

Functional role of phospholipids in the nuclear events.

This review presents the structural and functional role of phospholipids in chromatin and nuclear matrix as well as the difference in composition and turnover compared to those present in the nuclear membrane. Nuclei have a very active lipid metabolism which seems to play an important role in the transduction of the signals to the genome in response to agonists acting at the plasma membrane level. The evidence on the presence of phospholipid-calcium-dependent protein kinase C (PKC) in nuclei and enzymes of phospholipids turnover is given. Protein kinase C interacts with nuclear phosphoinositol and sphingomyelin cycles products. This fact evidences about possibility that signal transduction events could also occur at the nuclear level during induction of cell proliferation, differentiation and apoptosis.

Animals↗

Imbalance in the enzymatic system of production and consumption of active oxygen species in liver of AKR mice with spontaneous leucosis.

Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism.

Aging↗

Changes in superoxide production rate and in superoxide dismutase and glutathione peroxidase activities in subcellular organelles in mouse liver under exposure to low doses of low-intensity radiation.

The functioning of the antioxidant system in mouse liver at increased stationary concentration of active oxygen species induced by whole-body chronic exposure of mice to gamma-irradiation (137Cs, 0.6 cGy/day, 9 days) was studied. Synchronous changes (growth with an extreme) in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are found that may be considered as evidence in favor of maintenance of regulatory links in the antioxidant system of liver. The superoxide production rate in microsomes and nuclei also changed with an extreme with the rise in accumulated radiation dose. In microsomes the superoxide production rate reached a maximum at lower doses than the activity of Cu,Zn-SOD did. In nuclei the increase in superoxide production rate was not compensated by the rise in Cu,Zn-SOD activity within the studied dose range. The findings indicate some imbalance between production and consumption of superoxide radicals in microsomes and nuclei; in mitochondria these processes are balanced, leading to more resistance to low-dose irradiation.

Animals↗

[Certain biochemical blood markers in the process of cholinergic therapy in Alzheimer's disease].

Acetylcholinesterase (AChE) activity and parameters of the system of regulation of lipid peroxidation (LPO) were estimated in blood of patients with Alzheimer's disease (AD) during therapy with amiridine and gliatiline. It was found that the therapy was accompanied by inhibition of AChE activity. A significant correlation was observed between clinical efficiency and changes of AChE activity. AD was characterised by essential changes in LPO parameters: the level of the primary products of oxidation was increased three times with a sharp increase (seven times) of total unsaturation of lipids. A significant correlation was found between AChE activity and the level of the primary products of oxidation in blood erythrocytes of AD patients before and after therapy with amiridine and gliatiline.

Aged↗

The role of tocopherols in biomembrane lipid peroxidation.

The rate constants of elementary reactions of oxidation inhibition by tocopherols of different structures (peroxy radical destruction by antioxidant molecules, interaction of inhibitor radicals with one another and with oxidation substrate) are discussed. In contrast with most synthetic phenol antioxidants, tocopherols exhibit a high affinity to peroxy radicals (the rate constants for their reactions with these radicals are one or two orders of magnitude greater than those for reactions involving most synthetic phenols: they possess a fairly high stability of phenoxyl radicals formed and activity in the reaction of oxidation-chain transfer). The activity of tocopherol radicals in chain transfer reactions depends on their structure and manifests itself in a marked dependence of the extent of inhibition on oxidation conditions and the antioxidant concentration, up to an opposite effect. This can be used to control the oxidation rate: the radicals formed from tocopherols can serve as a buffer maintaining the oxidation rate at a certain level in systems with different antioxidant concentrations (concentration control) and with substrates of various unsaturation extent (substrate control). Tocopherols exhibit a unique set of properties which allow them to control the rate of lipid peroxidation and the physico-chemical properties of biological membranes. This dual effect provides the feedback relations and thereby maintains homeostasis in the organism.

Animals↗

Natural (alpha-tocopherol) and synthetic (phenosan potassium salt) antioxidants regulate the protein kinase C activity in a broad concentration range (10(-4)-10(-20) M).

The effects of natural lipid-soluble antioxidant, alpha-tocopherol (alpha-TP), and the synthetic water-soluble antioxidant, phenosan potassium salt (Ph-K), in a broad range of concentrations down to ultralow doses (10(-4)-10(-20) M) on the activity of protein kinase C (PKC) have been studied. It was shown that alpha-TP is a potent inhibitor of the rabbit heart enzyme: the maximum extent of inhibition is 80%. The effects of alpha-TP on the main kinetic parameters of the PKC activity differ at the alpha-TP physiological (10(-4) M) and ultralow (10(-14) M) concentrations: at 10(-14) M, alpha-TP acts as an allosteric inhibitor with Hill's coefficient about 2 and doubles the PKC affinity to the substrate (histone H-1). It was concluded that alpha-TP is more efficient inhibitor at ultralow concentration. Ph-K added to normal (A7r5 rat vascular smooth muscle cells, VSMC) and tumor cells (Saos-2 human osteosarcoma) growing in a culture has been found to be a PKC superactivator. The maximum activation is 400-500%, which is more than two times as high as the effect of the best activator of this enzyme, phorbol ester (TPA). It was demonstrated that irrespective of the effector action (activation or inhibition), the dose-effect curves are of the bimodal type with two maxima at the high (or physiological) (10(-4)-10(-7) M) and ultralow (10(-14)-10(-19) M) concentrations of the antioxidants and the so-called "silence zones" between them, in which the effect of antioxidants is significantly reduced or absent (tumor cells). For the first time, these bimodal curves were observed at the enzyme level. The results obtained are discussed considering various hypotheses of the effect of ultralow doses of biologically active compounds and the PKC activity regulation in normal and tumor cells by the antioxidants.

Animals↗

Phorbol ester at concentrations 10(-18)-10(-7) M inhibits lipid peroxidation in rat brain plasma membranes via activation of protein kinase C.

We studied the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and protein kinase C (PKC) in a broad range of concentrations (10(-18)-10(-7) M) on lipid peroxidation (LP) in rat brain plasma membranes. TPA and PKC were shown to inhibit LP, the concentration curves had two maxima at 10(-15) M and 10(-12) M for TPA and at 10(-16) M and 10(-13) M for PKC. The combined action of TPA (10(-12) M) and PKC (10(-16) M) resulted in a synergic inhibition of LP. These data suggest PKC to have two (kinase and antioxidative) enzymatic activities. The properties of TPA as an LP inhibitor (via activation of PKC) and tumour promoter (inhibition of LP is a necessary step of tumour promotion) can be explained based on this suggestion.

Animals↗