A. B. Gapeyev

The role of fatty acids in anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation

The effects of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR; 42.2 GHz, 0.1 mW/cm(2) , exposure duration 20 min) on the fatty acid (FA) composition of thymic cells and blood plasma in normal mice and in mice with peritoneal inflammation were studied. It was found that the exposure of normal mice to EHF EMR increased the content of polyunsaturated FAs (PUFAs) (eicosapentaenoic and docosapentaenoic) in thymic cells. Using a model of zymosan-induced peritoneal inflammation, it was shown that the exposure of mice to EHF EMR significantly increased the content of PUFAs (dihomo-γ-linolenic, arachidonic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic) and reduced the content of monounsaturated FAs (MUFAs) (palmitoleic and oleic) in thymic cells. Changes in the FA composition in the blood plasma were less pronounced and manifested themselves as an increase in the level of saturated FAs during the inflammation. The data obtained support the notion that MUFAs are replaced by PUFAs that can enter into the thymic cells from the external media. Taking into account the fact that the metabolites of PUFAs are lipid messengers actively involved in inflammatory and immune reactions, we assume that the increase in the content of n-3 and n-6 PUFAs in phospholipids of cellular membranes facilitates the realization of anti-inflammatory effects of EHF EMR.

Hydrogen peroxide induced by modulated electromagnetic radiation protects the cells from DNA damage

It is believed that non-ionizing electromagnetic radiation (EMR) and low-level hydrogen peroxide (H2O2) may change nonspecific resistance and modify DNA damage caused by ionizing radiation. To check this assumption, the combined effects of extremely high-frequency EMR (EHF EMR) and X-rays on induction of DNA damage in mouse whole blood leukocytes were studied. The cells were exposed to X-rays with or without preliminary treatment with EHF EMR or low-level H2O2. With the use of enhanced chemiluminescence, it was shown for the first time that pulse-modulated EHF EMR (42.2 GHz, incident power density of 0.1 mW/cm2, exposure duration of 20 min, modulation frequency of 1 Hz) induced H2O2 at a concentration of 4.6 ± 0.3 nM L−1 in physiological saline. With the use of an alkaline comet assay, it was found that the exposure of cells to the pulse-modulated EHF EMR, 25 min prior to treatment with X-rays at a dose of 4 Gy reduced the level of ionizing radiation-induced DNA damage. Continuous EHF EMR was inefficient. In turn, it was shown that low-level H2O2 (30–500 nM L−1) protected the cells against X-irradiation. Thus, the mechanisms of radiation protective effect of EHF EMR are connected with the induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated EHF EMR.

Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue

Abstract Purpose: To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Materials and methods: Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. Results: It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. Conclusions: The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

Changes in the chromatin structure of lymphoid cells under the influence of low-intensity extremely high-frequency electromagnetic radiation against the background of inflammatory process

Using the alkaline single cell gel electrophoresis technique (comet assay), changes in chromatin structure of peripheral blood leukocytes and peritoneal neutrophils have been studied in mice exposed to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after induction of inflammation) against the background of the systemic inflammatory process. It was revealed that the exposure of mice with the developing inflammation leads to a pronounced decrease in the level of DNA damage to peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the changes in the chromatin structure of lymphoid cells have a genoprotective character in the inflammatory process and can underlie the mechanisms of realization of antiinflammatory effects of the electromagnetic radiation.

Impact of biologically relevant anions on reactive oxygen species formation in water under the action of non-ionizing physical agents

The influence of biologically relevant anions (succinate, acetate, citrate, chloride, bicarbonate, hydroorthophosphate, dihydroorthophosphate, nitrite, nitrate) on the formation of hydrogen peroxide and hydroxyl radicals in water was studied under the effect of non-ionizing radiation: heat, laser light with a wavelength of 632.8 nm, corresponding to the maximum absorption of molecular oxygen, and electromagnetic radiation of extremely high frequencies. It has been established that various anions may both inhibit the formation of reactive oxygen species and increase it. Bicarbonate and sulfate anions included in the biological fluids and medicinal mineral waters have significant, but opposite effects on reactive oxygen species production. Different molecular mechanisms of reactive oxygen species formation are considered under the action of the investigated physical factors involving these anions, which may influence the biological processes by signal-regulatory manner and provide a healing effect in physical therapy.

Changes in fatty acid composition of thymus cells, liver, blood plasma, and muscle tissue in mice with solid Ehrlich carcinoma

The fatty acid composition of thymus cells, liver, blood plasma, muscle tissue, and tumor focus has been studied in mice with solid Ehrlich carcinoma. The tumor growth in the mice was associated with an increase in the total content of monounsaturated fatty acids in all organs and tissues studied and with a decrease in the total amount of polyunsaturated fatty acids in all tissues except blood plasma. The tumor tissue was characterized by increased levels of monounsaturated fatty acids in comparison with their levels in organs and tissues of intact animals. In the thymus of tumor-bearing mice, the contents of myristic and palmitic saturated fatty acids, which are associated with activation of the T-cell immunity, were increased. The most expressed and considerable changes in the fatty acid composition during tumor growth were observed in the muscle tissue of the animals. A possible role of changes in the fatty acid composition in the investigated organs and tissues of tumor-bearing mice in the organism’s response to tumor growth is discussed.

Comparative Study of Anti-Inflammatory Effects of Low-Intensity Extremely High-Frequency Electromagnetic Radiation and Diclofenac on Footpad Edema in Mice

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was compared to the action of sodium diclofenac on zymosan-induced footpad edema in NMRI mice. Diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg was injected intraperitoneally (ip) 30 min after zymosan injection. The mice were whole-body exposed to EHF EMR (42.0 GHz, 0.1 mW/cm2) for 20 min at 1 h after zymosan injection. Inflammation was assessed over 3–8 h after initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Diclofenac caused a dose-dependent anti-inflammatory effect. Doses of 5–20 mg/kg reduced the footpad edema on the average by 26% as compared to the control. Hyperthermia decreased with increasing in a dose of diclofenac, and at a dose of 20 mg/kg decreased by 60% compared to control. EHF EMR reduced both the footpad edema and hyperthermia by about 20% that was comparable with the effect of single therapeutic dose of diclofenac (3–5 mg/kg). Combined action of diclofenac and EHF EMR exposure caused a partial additive effect. The results obtained suggest that the adjunctive use of low-intensity EHF EMR with non-steroid anti-inflammatory drugs can provide more pronounced therapeutic effects.

NONLINEAR PROCESSES OF INTRACELLULAR CALCIUM SIGNALING AS A TARGET FOR THE INFLUENCE OF EXTREMELY LOW-FREQUENCY FIELDS

Theoretical analysis of peculiarities of reception of weak extremely low-frequency periodic signals by calcium-dependent intracellular regulatory systems was performed on the reduced “minimal” model for calcium oscillations suggested by Goldbeter et al. (Proc. Natl. Acad. Sci. USA 87, 1461–1465, 1990). The model considered the following calcium-dependent processes: the rise in intracellular free calcium concentration ([Ca2+]i) due to calcium ionophore A23187 action on a cell, activation of the Ca2+ entry through calcium channels in the plasma membrane by the initial rise in [Ca2+]i, and the Ca2+ release from intracellular stores by the calcium-induced calcium release mechanism. Calcium channels of plasma membrane were chosen as a target for the modulating signal and an additive noise influence in the model. An increase in [Ca2+]i under the influence of the modulating signal was demonstrated to depend not only on the amplitude and frequency of this signal, but also on the phase of the signal with respect to a momentary chemical stimulation of the cell. Such an effect was found only at high strengths of chemical stimulation and with a particular sequence of delivery of the chemical and electromagnetic stimuli. An increase in noise intensity led to magnification of the mean level of [Ca2+]i in a narrow frequency range by the mechanism of stochastic resonance. Under the influence of a modulating periodic signal, the gradual increase in strength of chemical stimulation induced a system transition from regular to chaotic behavior, and then to induced periodic oscillations. A boundary of the transition from chaotic to periodic oscillations corresponded to a “threshold” of sensitivity of calcium-dependent intracellular signaling systems on [Ca2+]i to the influence of the modulating signal. Results of the theoretical analysis led us to conclude that the narrow-band response of a system to an external electromagnetic signal is determined purely by nonlinear properties of the system.

Modifying effects of low-intensity extremely high-frequency electromagnetic radiation on content and composition of fatty acids in thymus of mice exposed to X-rays.

Abstract Purpose: The effects of extremely high-frequency electromagnetic radiation (EHF EMR) on thymus weight and its fatty acids (FA) content and FA composition in X-irradiated mice were studied to test the involvement of FA in possible protective effects of EHF EMR against ionizing radiation. Materials and methods: Mice were exposed to low-intensity pulse-modulated EHF EMR (42.2 GHz, 0.1 mW/cm2, 20 min exposure, 1 Hz modulation) and/or X-rays at a dose of 4 Gy with different sequences of the treatments. In 4–5 hours, 10, 30, and 40 days after the last exposure, the thymuses were weighed; total FA content and FA composition of the thymuses were determined on days 1, 10, and 30 using a gas chromatography. Results: It was shown that after X-irradiation of mice the total FA content per mg of thymic tissue was significantly increased in 4–5 h and decreased in 10 and 30 days after the treatment. On days 30 and 40 after X-irradiation, the thymus weight remained significantly reduced. The first and tenth days after X-rays injury independently of the presence and sequence of EHF EMR exposure were characterized by an increased content of polyunsaturated FA (PUFA) and a decreased content of monounsaturated FA (MUFA) with unchanged content of saturated FA (SFA). Exposure of mice to EHF EMR before or after X-irradiation prevented changes in the total FA content in thymic tissue, returned the summary content of PUFA and MUFA to the control level and decreased the summary content of SFA on the 30th day after the treatments, and promoted the restoration of the thymus weight of X-irradiated mice to the 40th day of the observations. Conclusions: Changes in the content and composition of PUFA in the early period after treatments as well as at the restoration of the thymus weight under the combined action of EHF EMR and X-rays indicate to an active participation of FA in the acceleration of post-radiation recovery of the thymus by EHF EMR exposure.

Responses of thymocytes and splenocytes to low-intensity extremely high-frequency electromagnetic radiation in normal mice and in mice with systemic inflammation

Changes in T cell subsets and expression of cytokine genes in thymocytes and splenocytes after exposure of BALB/c mice to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, exposure duration 20 min) under normal conditions and in systemic inflammation were studied using flow cytometry and the methods of reverse transcription and real-time polymerase chain reaction. It was found that the number of CD4+ and CD8+ T cells statistically significantly increased in the thymus and considerably decreased in the spleen of exposed animals. Apparently, the exposure of animals leads to an intensification of the host defense, by activating the T-cellular immunity. As for effector functions, the increased expression of IL-1β and IFNγ genes in thymocytes and essentially enhanced expression of IL-1β, IL-10, and TNFα genes in splenocytes were observed in mice exposed against the background of a progressive inflammatory process. The experimental data obtained specify that the directed (anti-inflammatory) response of an organism to a specific combination of effective exposure parameters of electromagnetic radiation can be realized by the activation of particular immunocompetent cells and changes in the cytokine profile.