Decrease in the intensity of the cellular immune response and nonspecific inflammation upon exposure to extremely high frequency electromagnetic radiation

The effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2, 20 min daily) on cell-mediated immunity and nonspecific inflammatory response in mice was studied. The intensity of cell-mediated immune response in the reaction of delayed-type hypersensitivity and nonspecific inflammation was estimated by a relative increase in the thickness of foot pad after immunization of animals by sheep red blood cells or zymosan. It was shown for the first time that the radiation reduces both immune and nonspecific inflammatory responses. It was shown with the use of models of acute inflammation and full-thickness skin wounds that EHF EMR suppresses the nonspecific inflammatory response but does not influence the duration of the pathological process. We suppose that the basis of the effects revealed is the modification of functional activity of phagocytic cells under the influence of EHF EMR. The results suggest that some therapeutic effects of EHF EMR can be realized via the inhibition of inflammatory processes.     

Effects of low-intensity extremely high frequency electromagnetic radiation on chromatin structure of lymphoid cells in vivo and in vitro

Using a comet assay technique, it was shown for the first time that low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) in vivo causes oppositely directed effects on spatial organization of chromatin in cells of lymphoid organs. In 3 hrs after single whole-body exposure of NMRI mice for 20 min at 42.0 GHz and 0.15 mW/cm2, an increase by 16% (p < 0.03 as compared with control) and a decrease by 16% (p < 0.001) in fluorescence intensity of nucleoids stained with ethidium bromide were found in thymocytes and splenocytes, respectively. The fluorescence intensity of stained nucleoids in peripheral blood leukocytes was not changed after the exposure. The exposure of cells of Raji hunan lymphoid line and peripheral blood leukocytes to the EHF EMR in vitro induced a decrease in fluorescence intensity by 23% (p < 0.001) and 18% (p < 0.05), respectively. These effects can be determined by changes in a number of physiological alkali-labile sites in DNA of exposed cells. We suggested that the effects of low-intensity EHF EMR on the immune system cells are realized with the participation of neuroendocrine and central nervous systems.     

Suppression of nonspecific resistance of the body under the effect of extremely high frequency electromagnetic radiation of low intensity

The dynamics of leukocyte number and functional activity of peripheral blood neutrophils under whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.15 mW/cm2, 20 min daily) was studied. It was shown that the phagocytic activity of peripheral blood neutrophils was suppressed by about 50% (p < 0.01 as compared with the sham-exposed control) in 2-3 h after the single exposure to EHF EMR. The effect persisted for 1 day after the exposure, and then the phagocytic activity of neutrophils returned to the norm within 3 days. A significant modification of the leukocyte blood profile in mice exposed to EHF EMR for 5 days was observed after the cessation of exposures: the number of leukocytes increased by 44% (p < 0.05 as compared with sham-exposed animals), mostly due to an increase in the lymphocyte content. The supposition was made that EHF EMR effects can be mediated via the metabolic systems of arachidonic acid and the stimulation of adenylate cyclase activity, with subsequent increase in the intracellular cAMP level. The results indicated that the whole-body exposure of healthy mice to low-intensity EHF EMR has a profound effect on the indices of nonspecific immunity.     

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.     

Effects of the blockade of the system of opioid peptides on changes in emotional/behavioral reactions of rats induced by the action of extrahigh-frequency electromagnetic radiation in the norm and under conditions of hypokinetic stress

We studied the effects of pharmacological blockade (by injections of naloxone) of the system of opioid peptides on changes in emotional/behavioral reactions of rats in the open-field test. These changes were caused by the isolated action of low-intensity electromagnetic radiation (EMR) of extrahigh frequency (EHF) and its combination with experimentally induced hypokinetic stress. We conclude that one of the mechanisms of physiological effects of low-intensity EHF EMR is an increase in the functional activity of the system of regulatory opioid peptides; this results in adaptive modifications of the emotional/behavioral reactions under new conditions of the open-field test and provide an anti-stress effect under conditions of hypokinetic stress. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 52–60, January–February, 2006.     

Roles of different neurochemical systems in mechanisms underlying the antinociceptive effect of extrahigh-frequency electromagnetic radiation

We studied the effect of low-intensity extrahigh-frequency (EHF) electromagnetic radiation (EMR) on the duration of a pain behavioral reaction in rats under conditions of experimental induction of tonic pain (formalin test). The antinociceptive effect of EHF irradiation was modulated by suppression of the activity of a few neurochemical systems resulting from the blockade of receptors of opioid peptides, α-and β-adrenoreceptors, receptors of dopamine and melatonin, as well as from inhibition of serotonin synthesis. We demonstrated that all the respective neurochemical systems are to a certain extent involved in the mechanisms underlying the analgesic action of EHF EMR. Within an early phase of pain stress, functioning of the opioidergic and noradrenergic systems and the effects of melatonin play leading roles, while the activity of the serotonergic system plays such a role within the second (tonic) phase. Neirofiziologiya/Neurophysiology, Vol. 39, No. 2, pp. 165–173, March–April, 2007.     

Modifications of Motor Asymmetry in Rats under the Influence of Low-Intensity Extra High-Frequency Electromagnetic Radiation in the Norm and under Stress Conditions

We studied modifications of motor asymmetry in rats with different motor lateralization (dextrals, sinistrals, and ambidextrals) induced by low-intensity extra high-frequency (EHF) electromagnetic radiation (EMR), hypokinetic stress, and their combination. It was found that the development of hypokinetic stress in rats induced by limitation of their mobility results in a considerable decrease of the coefficient of motor asymmetry (up to inversion of its sign); this can be related to a decrease in the resistivity to stressing and adaptability of the organism to the influence of external factors. The influence of EHF EMR on the animals under conditions of both normal and limited motor activity resulted in an increase in the index of motor lateralization in animals of all phenotypic groups under study; probably, this helped to increase the adaptive capabilities of the organism. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 164–168, March–April, 2005.     

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/cm², 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. Bioelectromagnetics 32:388–395, 2011. © 2011 Wiley‐Liss, Inc.     

Features of anti‐inflammatory effects of modulated extremely high‐frequency electromagnetic radiation

Using a model of acute zymosan‐induced paw edema in NMRI mice, we test the hypothesis that anti‐inflammatory effects of extremely high‐frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1–0.7 mW/cm² and frequencies from the range of 42.2–42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti‐inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03–100 Hz did not lead to considerable changes in the effect level. On the contrary, at “ineffective” carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07–0.1 and 20–30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti‐inflammatory action of low‐intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed. Bioelectromagnetics 30:454–461, 2009. © 2009 Wiley‐Liss, Inc.     

Functional Activity of the Sympathoadrenal System and Behavioral Indices of Rats: Changes Induced by Millimeter-Range Electromagnetic Radiation

We examined the ability of low-intensity millimeter-range (mmR) electromagnetic radiation (EMR) to modify the functional activity of the sympathoadrenal system (SAS) and the behavioral reactions in intact rats and rats with an experimentally induced stress reaction. Adaptation of the organism to mmR EMR has been shown to limit SAS activation; this is considered one of the mechanisms of the antistressor effect of such radiation.     

Effect of millimeter band electromagnetic radiation on a culture of sensory neurons from the chick embryo

The effect of extra-high frequency electromagnetic radiation (EHF EMR) on the development of organotypical culture of the spinal ganglia of a 9–10 day-old chick embryo was investigated. EMR with a wavelength of 5.6 mm and a rate of flow density <1.0, 4.0, and >100 mW/cm² was used. The stimulating action of EMR at rate of flow density of 4.0 mW/cm², manifested in intensification of the growth of neurites of sensory neurons and the proliferation of the peripheral glia, was observed. EHF EMR with a density >100 mW/cm² exerted inhibitory influence. The possibility of using the stimulating effect of EHF EMR in medical practice for intensifying regeneration in pathology and after trauma of the peripheral nervous system is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 175–179, May–June, 1993.     

Role of phospholipase A2 and epoxygenase in inhibition of respiration burst in neutrophils by low intensity radiation of extremely high frequency

The role of some components of the phospholipid metabolism in the activation of neutrophil respiratory burst and its inhibition by electromagnetic radiation (EMR) of extremely high frequencies (EHF) was studied. It was shown that EHF EMR has effect on cells with a high sensitivity to the inhibitor of phospholipase A2 4-bromophenacyl bromide. However, againsts the background of the inhibitor, the effect of EHF EMR was not observed on cells with either high or low sensitivity to the inhibitor. EHF EMR was also inefficient with cells pretreated with proadifen, an inhibitor of epoxygenase (cytochrome P-450). The results obtained suggest that the effect of EHF EMR manifests itself in cells with a high activity of phospholipase A2 and is realized with the participation of epoxygenase metabolites of arachidonic acid.     

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR.     

Signal transduction in cells of the immune system in microgravity

Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.     

Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits

The number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems is still increasing. Until now no satisfactory mechanism has been proposed to explain the biological effects of this radiation. Oxygen free radicals may play a role in mechanisms of adverse effects of EMR. This study was undertaken to investigate the influence of electromagnetic radiation of a digital GSM mobile telephone (900 MHz) on oxidant and antioxidant levels in rabbits. Adenosine deaminase, xanthine oxidase, catalase, myeloperoxidase, superoxide dismutase (SOD) and glutathione peroxidase activities as well as nitric oxide (NO) and malondialdehyde levels were measured in sera and brains of EMR-exposed and sham-exposed rabbits. Serum SOD activity increased, and serum NO levels decreased in EMR-exposed animals compared to the sham group. Other parameters were not changed in either group. This finding may indicate the possible role of increased oxidative stress in the pathophysiology of adverse effect of EMR. Decreased NO levels may also suggest a probable role of NO in the adverse effect.     

Model analysis of nonlinear modification of neutrophil calcium homeostasis under the influence of modulated electromagnetic radiation of extremely high frequencies

The problem of resonance effects of electromagnetic radiation (EMR) on biological objects remained unsolved till now. Previously we demonstrated that low-intensity amplitude-modulated EMR of extremely high frequencies (EHF) modified the activity of mouse neutrophils in the synergistic reaction of calcium ionophore A23187 and phorbol ester PMA. The EHF EMR influence on the neutrophils was significant at the carrier frequencies of radiation within a narrow range of 41.8–42.05 GHz and at the modulation frequency of 1 Hz. The purpose of the work was the analysis of frequency-dependent modification of intracellular free calcium concentration ([Ca²⁺]_i) by modulated EHF EMR on the basis of a special model for [Ca²⁺]_i oscillations in the neutrophils. The calcium channels of plasma membrane were chosen as the action target of external modulation in the model. The computer simulation demonstrated the rise in [Ca²⁺]_i at the influence of the external field with a threshold dependence on the modulation amplitude. The effect depended heavily on a sequence of delivery of the chemical and electromagnetic stimuli. The narrow-band rise in [Ca²⁺]_i had a phase-frequency dependence. With the modulation amplitudes exceeding the threshold value, the rise in [Ca²⁺]_i of more than 50% of the initial level was observed at the frequency of about 1 Hz and in the phase range of 0.3–2.5 radians. The results of the model analysis are in good correspondence with the experimental data obtained before, namely, with the resonance modification of the neutrophil activity at the modulation frequency of 1 Hz and with the presence of the effect only at high concentrations of calcium ionophore.     

Antinociceptive effects of low-intensity extrahigh-frequency electromagnetic radiation

We studied the effect of low-intensity extrahigh-frequency (EHF) electromagnetic radiation (EMR) on changes of behavior phenomena in rats observed under conditions of experimentally induced tonic somatic, visceral, and acute thermal pain. Preliminary irradiation of the animals with EHF EMR was found to exert clear antinociceptive effects. Decreases in the intensity of pain reactions were observed under conditions of both single and repeated irradiation sessions. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 331–341, July–August, 2006.     

Pharmacological analysis of the antiinflammatory effects of low-intensity extremely-high-frequency electromagnetic radiation

The antiinflammatory effect of low-intensity extremely-high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm²) was studied in comparison to the effects of the antiinflammatory drug sodium diclofenac and the antihistamine clemastine in acute inflammatory reaction in mice of NMRI outbred stock. The local inflammatory reaction was induced by intraplantar injection of zymosan to the left hind paw. Intraperitoneal injections of 2, 3, 5, 10, and 20 mg/kg of sodium diclofenac or 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg of clemastine were made 30 min after the initiation of inflammation. An hour after the initiation of inflammation, animals were whole-body exposed to EHF EMR for 20 min. The inflammatory reaction was assessed 3–8 h after initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac (5–20 mg/kg) reduced the exudative edema by ～26% compared to the control. Hyperthermia of the inflamed paw decreased by 60% with an increase in the diclofenac dose to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by ～20%. This was comparable to the effect of a single therapeutic dose of diclofenac (3–5 mg/kg). The combination of diclofenac and exposure to EHF EMR produced a partial additive effect. Clemastine (0.02–0.4 mg/kg) did not affect the exudative edema, but at a dose of 0.6 mg/kg, edema was reduced by 14–22% five to eight hours after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses 0.02–0.2 mg/kg and did not affect the hyperthermia at doses 0.4 and 0.6 mg/kg. A combination of clemastine and EHF EMR exposure resulted in a dose-dependent abolishment of the antiinflammatory effect of EHF EMR. Our results suggest that both arachidonic acid metabolites and histamine are involved in the achievement of the antiinflammatory effects of low-intensity EHF EMR.     

Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation

The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity     

Electromagnetic Radiation Influence on Nonlinear Charge and Energy Transport in Biosystems

The influence of electromagnetic radiation (EMR) on charge and energy transport processes in biological systems is studied in the light of the soliton model. It is shown that in the spectrum of biological effects of EMR there are two frequency resonances corresponding to qualitatively different frequency dependent effects of EMR on solitons. One of them is connected with the quasiresonance dynamic response of solitons to the EMR. At EMR frequencies close to the dynamic resonance frequency the solitons absorb energy from the field and generate intensive vibrational modes in the macromolecule. The second EMR resonance is connected with soliton decay due to the quantum mechanical transition of the system from the bound soliton state into the excited unbound states.