Antioxidants as radioprotecting agents for low-level irradiation

Burlakova, E. B.; Goloshchapov, A. N.; Konradov, A. A.; Molochkina, E. M.; Treshchenkova, Yu.A; Шишкина, Л. Н.

doi:10.1016/s0531-5131(01)00859-7

Cited by 5 publications

(9 citation statements)

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“…Indeed, as was established in some studies analyzed in review [9], the best positive results in vari ous biochemical and medical studies of the effect of potassium phenosan were obtained when it was used at concentrations of 10 -5 to 10 -6 , 10 -14 , and 10 -18 M. Let us compare the results of the effect of the natural anti oxidant α tocopherol on biological membranes, which were obtained by us earlier [1,2], and the effect of the synthetic antioxidant potassium phenosan. The comparison showed that (1) potassium phenosan, similarly to α tocopherol, has a stabilizing effect on the buried regions of plasma membrane and endoplas mic reticulum lipids in nearly the entire concentration range studied (10 -23 to 10 -3 M); (2) dose dependences of effects of both agents have a polymodal nonlinear character; and (3) potassium phenosan affects mostly plasma membranes, whereas α tocopherol has a greater effect on endoplasmic reticulum.…”

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confidence: 68%

Dose dependences of lipid microviscosity of biological membranes induced by synthetic antioxidant potassium phenosan salt

Palmina

Chasovskaya

Belov

et al. 2012

Dokl Biochem Biophys

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Earlier, we demonstrated for the first time that the natural antioxidant α tocopherol in a wide concentra tion range can modify the structure of different lipid regions in the endoplasmic reticulum and plasma membranes of hepatocytes in experiments in vitro [1,2]. Despite the biochemical and functional differences between endoplasmic reticulum and plasma mem branes, they are characterized by similar polymodal non linear dose dependences of the effects of α toco pherol on the rigidity of superficial (~8 Å) and micro viscosity of buried (~20 Å) lipid bilayer regions. Such patterns are typical for biologically active substances, showing an effect over a wide concentration range, including ultralow doses [1,2]. The polymodality of dose dependences is associated with the statistically significant effects of α tocopherol in three concentra tion ranges. It is assumed that three possible mecha nisms of action may underlie the effect of this com pound depending on its concentration: insertion into the membrane, interaction with specific binding sites, and the information transfer through the layers of water with special physical and chemical properties [1][2][3]. It is known that the main physicochemical characteristic of antioxidants is their ability to inhibit lipid peroxidation (LPO) both in vitro and in vivo, the regulatory system of which includes the microviscosity of lipids [4].In view of above, a question arises as to what are the common and distinctive features of the effects of nat ural and synthetic agents at ultralow doses and whether the relationship between the ability of antiox idants to inhibit LPO and modify the structure of bio logical membranes is retained when they are used at ultralow doses. To answer this question, we assessed the effect of potassium salt of β (4 hydroxy 3,5 diter tbutylphenyl) propionic acid (potassium phenosan), a synthetic antioxidant, in a wide concentration range on the lipid microviscosity of EPR and PM of hepato cytes.The study was performed with 100 F 1 mice (C 57 BL × DBA 2 ). Potassium phenosan solutions were prepared by successive tenfold dilutions of the initial solution (10 -3 M) with distilled water followed by shaking on a shaker for 1 min. Plasma membrane and endoplasmic reticulum were isolated from mouse hepatocytes by centrifugation by the method of Loten [5]. Mice were sacrificed by decapitation. Protein concentration was determined by the method of Lowry [6]. The parameters characterizing the struc ture of membranes were calculated from the spectra obtained at 293 K on a Bruker 200D EPR spectrome ter (Germany) by the spin probe method [7]. The microviscosity of buried lipid bilayer regions (~20 Å) was estimated using 16 doxylstearic acid (С 16 ). The membrane microviscosity near the С 16 probe was eval uated on the basis of the rotational correlation time of the probe τ С1 and τ С2 , which was determined by the formulas for rapid anisotropic rotation of radicals [7]. The absolute values of parameters τ С1 and τ С2 in the control and after the treatment with potass...

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confidence: 68%

Dose dependences of lipid microviscosity of biological membranes induced by synthetic antioxidant potassium phenosan salt

Palmina

Chasovskaya

Belov

et al. 2012

Dokl Biochem Biophys

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“…Some of them are discussed below: Figure 2 shows the type of dependence of human mortality (caused by leukemia) on the equivalent dose d. As the death rate К the ratio of the number of deaths per 100000 person-years to the number of deaths caused by the equivalent dose of about 23 mSv is used. The curve is based on the data collected under Burlakova's guidance [2,8]. It rats were exposed to low-frequency alternating magnetic field.…”

Section: Introductionmentioning

confidence: 99%

The Physical Aspect of Action of Biologically Active Substances in Ultra- Low Doses and Low-Intensity Physical Factors on Biological Objects: Spin Supercurrents

2013

Altern Integ Med

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Introduction1. The non-monotonic, polymodal dose-effect dependence. In most cases the activity maxima are observed within definite ranges of doses, which are separated by so-called "dead zones". In some cases, the same effects are produced by low-doses differing in 5 to 8 orders of magnitude. There are also cases where a change in the "sign" of the effect is observed in the dose dependence. Figures 1-4 give some examples of this feature. Figure 1 shows the type of variation of the content of protein р53 with mice of F1 line as a function of dose D of the injected BAS, namely, antioxidant phenosan [6,7]. The value D=10 -14 mole/kg corresponds to an ultra-low dose.is noteworthy that there is a range of values of d (at about 75 mSv) where the magnitude of К is less than that for the background value of d (about 2 mSv). It may be said that ultra-low doses of ionizing radiation in this range has a therapeutic effect.

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“…Thus, we obtained dose depen dences typical of the compounds showing effect at super low doses (SLD) [3,4]. To reveal the mecha nism of action of biologically active compounds (BACs), including PP, at super low doses, it is a signif icant question about the target of this agent, in partic ular, whether PP acts directly to the lipid bilayer or it affects indirectly via proteins and receptors.…”

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confidence: 99%

“…Since the majority of experiments to study these effects have been conducted for rather complex living systems-organisms, cell populations, tissues, cells, and cell membranes comprising a wide range of regu latory cell systems-concepts have been primarily put forward implying the presence of superaffine recep tors, the action of cascade mechanisms of signal amplification [4], the cell adaptation to a certain rela tively high concentration of substance, and the pres ence of fast and slow reactions with the substance added on this background which can have opposite effects [3,11].…”

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confidence: 99%

Physicochemical alterations in liposomes induced by low concentrations of synthetic antioxidant potassium phenosan

2013

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We have recently shown by spin probe ESR that synthetic antioxidant potassium β (4 hydroxy 3,5 di tert butylphenyl)propionate (potassium phenosan, PP) can modify the structural state of surface (8 Å) and deep lying (20-22 Å) regions of lipids of plasmatic membranes isolated from mouse liver cells in a wide concentration range (10 ⎯5 ⎯10 -21 M) in vitro [1,2]. Nonlinear bimodal dose-effect dependences were obtained for parameters that characterize the micro viscosity of lipid bilayer (τ c ) in the location region of nitroxyl fragment of 16 doxylstearic acid (С 16 ) probe and for ordering parameter (S) that characterizes the rigidity of surface lipid layers in the location area of 5 doxylstearic acid (С 5 ) probe.It was established that a statistically significant increase in τ c parameter was observed at the PP con centration of 10 -5 -10 -7 and 10 -18 -10 -19 M, while that in S parameter was detected at a concentration of 10 -6 -10 -7 and 10 -13 -10 -15 M. Effect maxima were separated by concentration ranges where PP had no effect on the studied physicochemical characteristics of biomembranes. Thus, we obtained dose depen dences typical of the compounds showing effect at super low doses (SLD) [3,4]. To reveal the mecha nism of action of biologically active compounds (BACs), including PP, at super low doses, it is a signif icant question about the target of this agent, in partic ular, whether PP acts directly to the lipid bilayer or it affects indirectly via proteins and receptors. There fore, the aim of this work is to study the effect of PP in a wide concentration range on the structural state and size of liposomes prepared from lipids extracted from plasmatic membranes (PM) of mouse liver cells.Experiments were carried out in 80 mice of F1(C57BLx. DBA2) line. PP solutions were prepared by serial tenfold dilution of a 10 -3 M stock solution of PP with distilled water followed by shaking with a shaker for 1 min. Plasmatic membranes of mouse liver cells were isolated by centrifugation according to the Loten procedure [5]. The mice were decapitated. Pro tein concentration was determined by the Lowry pro cedure [6]. Parameters that characterize the mem brane structure were calculated from spectra obtained at 293 K on a Bruker 200D ESR spectrometer (Ger many) by the spin probe method [7]; 16 doxylstearic acid (С 16 ) was used as the spin probe to study microvis cosity of deep lying regions of the lipid bilayer (~20 Å). Membrane microviscosity in the region of location of the С 16 probe was assessed from the rotational correla tion times of the probe τ c1 and τ c2 , which were deter mined from the formulas for fast anisotropic rotation of radicals [7]. The absolute values of τ c1 and τ c2 parameters, both in control and after treatment with PP, differed but the relative changes of these values were the same; therefore, the figures show the effects for τ c1 expressed as percentage of control.5 Doxylstearic acid (С 5 ) was used as a spin probe to study the rigidity of surface domains of membrane. The membrane rigidity i...

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Antioxidants as radioprotecting agents for low-level irradiation

Cited by 5 publications

References 1 publication

Dose dependences of lipid microviscosity of biological membranes induced by synthetic antioxidant potassium phenosan salt

Dose dependences of lipid microviscosity of biological membranes induced by synthetic antioxidant potassium phenosan salt

The Physical Aspect of Action of Biologically Active Substances in Ultra- Low Doses and Low-Intensity Physical Factors on Biological Objects: Spin Supercurrents

Physicochemical alterations in liposomes induced by low concentrations of synthetic antioxidant potassium phenosan

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