The model for study of influence Of magnetic fields on biological objects (within the Russian maglev project)

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Abstract


Aim: methodological aspects of the study influenced static magnetic fields (SMF) used in the technology "Russian Maglev" on the organisms are improved.

Materials and methods: organotypic culture of animal tissue fragments was studied under the influence of an experimental setup generating a homogeneous SMF with characteristics similar the "Russian Maglev".

Results: area index (AI) for liver, heart, prostate, renal tissue of explants in the control and under the action of SMF did not differ. SMF significantly reduces AI of explants the immune tissue of the spleen and the cerebral cortex.

Conclusions: 1. the influence of SMF has a negative impact on the proliferative activity in organotypic culture of the cerebral cortex and spleen; 2. the biological model for examination of influence SMF on organisms intended for approbation of means of physical protection is presented.


INTRODUCTION

The main attention in the modern scientific literature is paid to operational developments and problems of magnetic levitation transport systems, the energy analysis of the technologies used and developed, the search for optimal technical solutions for safety. The project "Russian Maglev" (RM) is used the system of static magnetic levitation in contrast to electrodynamic (Maglev) and electromagnetic (Transrapid) levitation systems [1]. In this regard, the issues of medical safety of the "RM" have special features, although in the overall structure of the problems they are given insufficient attention. Therefore, it is important to establish the locations and levels of field characteristics around the "RM", to conduct model medical and biological studies to establish the impact of non-radiation physical fields on various systems of the body, to develop evidence-based proposals and recommendations for the establishment of regulatory norms in this type of transport, to protect against harmful fields effects on passengers and service personnel.

The aim of this work was to study the characteristics of the main sources of static magnetic fields (SMF) used in the technology of "RM" and affecting the human body. The studies in organotypic tissue culture for the differentiated assessment of SMF impact on the organs of different mammalian systems were carried out. It should be noted that the cell and tissue cultures in biological research is increased common as relatively simple model systems is possible to successfully solve many problems the impact of various environmental factors on different organisms.

Organotypic tissue culture is the most appropriate and convenient method for a rapid quantitative assessment by level influenced physical factors on biological objects [2,3]. This is due to the change in the number of cells is the result of stimulation or inhibition of cell proliferation, and this change serves as a criterion for the primary integral assessment of biological activity, including SMF. The advantage of this method is that the explants retain the same hierarchical subordination of the cellular composition of the tissue, as well as in the whole body. In the organotypic culture the strictly dosed effect directly on the cells by SMF is possible to have. This excludes the effect of the whole body nervous, hormonal and other effects. The classical test system is the organotypic culture of various rat tissues.

MATERIALS AND METHODS

The effect of SMF on cell proliferation processes in organotypic tissue culture from different organs mature male rats of the Wistar population (“collection of laboratory mammals of different taxonomic affiliation”, Pavlov Institute of Physiology RAS supported by the program of bio-resource collections Federal Agency of Science Organizations from Russia) were studied. The 747 explants of the tissues of the cerebral cortex (n=182), spleen (n=184), kidney (n=95), heart (n=96), prostate (n=92) and liver (n=98) were studied in the experiments. Explants were placed in Petri dishes with a nutrient medium pH=7.2 containing saline (0.9 %) 50 ml, MEM 50 ml, fetal bovine serum 10 ml, glucose (5 %) 1 ml, gentamicin (4 %) 0.5 ml. Petri Dishes with explants were placed in a CO2 incubator at 36,8°C [4, 5].

The experimental Petri Dishes were exposed in a special camera with a magnetizing device consisting two magnetic poles-concentrators (flat ferrite magnets Y22H (Fe2O3SrCO3) with an anisotropic magnetic structure and a platform of non-magnetic material for placing Petri dish with explants of the studied tissue. Concentrators formed a spot of homogeneous SMF, the structure and the amount of induction was controlled by the device Teslameter f 4354/1 at the location studied tissue. The magnitude of the intensity and control of the uniformity of the field in the spot was established and regulated by the mutual location of the concentrators. The measurement error did not exceed 2.5 %. Petri dishes with samples of different tissues was placed between the working ends face of the magnet poles where were within three days at a constant temperature and atmosphere with a homogeneous SMF (~200 mT). The value of the SMF induction value in the experiment corresponds to the SMF intensity in the railway car of the project "RM" at one meter from the floor [6].

The data of two experiments for each tissue included the control Petri dishes without SMF exposure and experimental Petri dishes the with SMF were obtained. To quantify the impact of SMF on the development of explants used for morphometric method comparing the control and experimental Petri dishes. For this after the explants were visualized using a microtelevision attachment (series 10, MTN-13, Alpha-Telecom), was calculated area index (AI) using PhotoM 1.2 software.

In the cultivation there is migration cells into the growth zone (GZ) from the Central zone (CZ) of the explant estimated by AI calculating by the formula (1) relationships area (S) the explant (SGZ+CZ) to the area of the central zone ( SCZ).

AI=SGZ+CZSCZ (1)

Then, the values of AI were averaged separately for the control AIC and experimental dishes AIE. The Average value of AIC was taken as 100 %, and the difference of average values (ΔAI) expressed in percent by the formula (2), demonstrates the amount and direction of influence on proliferation of cells.

ΔAI=AIEAICAIC×100 % (2)

The reliability of the differences of AI explants in the control and experimental dishes after checking for compliance with the normal distribution of the data was evaluated using t criteria for independent samples. Statistically significant differences were taken at the level of p less than 0.05.

RESULTS AND DISCUSSION

According to previously studied and presented the characteristics of the main sources of SMF in the technology "RM" [6], the magnetic induction exposed to the human body increases from < 1 to 300 mT when approaching the source of MF from 0.7 to 0.1 m, respectively. The data obtained are compared with the current Russian normative and technical documents: SanPiN 2.2.4.3359-16 "Sanitary and epidemiological requirements for physical factors in the workplace" (unfortunately, the regulatory standards in the Russian Federation on transport have not yet been developed). According to the literature data, non-specific reaction by the type of General adaptation syndrome were caused in the human body after exposition of SMF. There is possible specific, similar to the meteotropic, reaction, proceeding with a change in vascular tone. There is a belief that the magnetic factor is not the direct cause of the disease, it only provokes it or contributes to the aggravation of the existing pathological process. People with meteosensitivity may have functional disorders that affect the quality of life. At the same time, the specific dynamics of physiological parameters in different people may be vary [7].

However, the results of screening studies exposure on different organs by SMF the same intensity in the literature could not be found. In addition, only a number of studies have described the study of the characteristics of SMF having the greatest biological effect. There is the most suitable method organotypic tissue culture for the screening study of the action of biologically active factors [8].

According our experimental data uniform SMF with induction of ~200 mT has different effects on the cells of different mammalian tissues. In the Table 1 presents the average values of AI for the explants organotypic tissues culture: liver, heart, prostate, kidneys and we can conclude that proliferative processes are not changed because the values of statistically not significant different from . While SMF depressed cell proliferation of immune spleen tissue and brain cells.

 

Table. The average values of AI for the explants organotypic tissues culture in control (AIC)  and experiment (AIE )

 

cerebral cortex

spleen

liver

renal

prostate

heart

 AIC,n.u.

1.6±0.26

1.98±0.62

1.67±0.67

2.11±0.78

1.37±0.2

1.79±0.37

 AIE,n.u.

1.29±0.12

1.6±0.34

1.66±0.3

1.76±0.32

1.36±0.2

1.78±0.19

Р-value

0.03

0.03

0.83

0.26

0.85

0.65

 

There is decreasing AIfor explants in the experiment compared to the control statistically significantly (P=0.03) for the tissues of the cerebral cortex (ΔPI= –19.7 %) and spleen (ΔPI= –18.9 %).

Despite the above results impact of SMF on living organisms and cells, the long-term practice of SMF application in medical procedures, for example MRI, allowed to publish the works, confirming the safety of SMF application [19, 20]. Although using relatively strong magnetic fields, such procedures can really be safe for patients due to the short duration of magnetic exposure. For the staff, the chronic action of SMF and other harmful factors, allows to neutralize compliance with Sanitary and epidemiological requirements that are non-specific to neutralize the action of SMF [18]. The presented data do not exclude the remote manifestations of SMF by induction 1T exposure for human health [21, 22], although no such effects have been found in other studies [23].

In according to above, there is important to search protection means to reduce the biological effect of SMF on passengers and service men using the transport system "RM". Therefore, in our work we have tried to present the testing model for various neutralization or decrease means of SMF biological effects with the organotypic tissue culture. For this in the 2nd series of experiments, the polypeptides with tissue-specific and stimulating proliferative effect were selected [23, 24] and were introduced into the culture medium for SMF undergone explants. The drug Cortexin® was added to medium of explants the cerebral cortex and Timalin® was added to medium of explants the spleen. These drugs were added at effective concentration 50 nG/ml. Figure 1 shows to decrease statistically not significant the number of AI (ΔAI= –12.3 %) under the action of Cortexin® in explants of the cerebral cortex (thus, the effect of SMF decreased overall by 9 %). The increase of AI statistically not significant was observed in the experimental compared to control the Petry dishes with explants of the spleen undergone combined effect of Thymalin® and SMF (ΔAI =+13.4 %).

 

Fig. The SMF influence on the cortex (1) and spleen (2) in isolation (dark bars) and in combination with Cortexin® and Timalin® respectively (light bars)

 

The data confirm the functional inhibition of proliferative activity explants of spleen and cerebral cortex under the influence of SMF and the normalization proliferative potential under the influence contained growth factors in the used drugs.

Our data have been compared with the other studied data, as the SMF with induction in the range from hundredth to hundreds of mT in the laboratory is created relatively easy. Currently, there is two main areas for scientist’s attention of research: the actioned mechanisms of SMF on living organisms are searched and the biological effects of weak SMF usually with adverse effects on the body are observed. We will discuss the latter direction in more detail. In a number of studies with MF with similar characteristics were obtained cellular effects. In all studies the inhibition of cell proliferation due to an increase in DNA damage when exposed to SMF induction 970 mT [9] or MF with a frequency of 50 Hz and induction 400 mT [10], stimulation of apoptosis MF with a frequency of 50 Hz and induction of 150 mT [11] and SMF with induction 1Т [13], increased transcription of genes in SMF with induction 100 mT [15] and damaging effect on the cell membrane with induction of SMF 100–300 mT [17] were described.

However, simple decrease as the induction level of SMF 10–1 000 times then the maximum permissible level (according to 2.2.4.3359-16 “Sanitary and epidemiological requirements to physical factors in working places”) does not neutralize the negative effects of SMF at the cells. According to the literature, enhancing proliferation due to inhibition of apoptosis in SMF with induction of 0.6 mT [12], decreasing the adhesive ability of white blood cells in SMF with induction of 0.05–10 mT [14], increasing the intracellular concentration of heat shock proteins in MF with a frequency of 50 Hz and induction of 10–140 µT [16] are observed. In this regard, there is our direction of research studying the damaging effects of MF with the value of induction and measured characteristics around the "RM".

CONCLUSION

It was shown, the people need for protection from MF of "RM" system. On the basis of the research listed in this article, the prospect of using the presented biological model in the development and testing of methods and measures to protect against the adverse effects of MF arising from the operation of the magnetic levitation transport system is created. After substantiation of medical and biological safety at the cellular level of technogenic MF system "RM", it is possible to conduct monitoring studies on real models [26].

The above data allowed us to draw the following conclusions:

  1. At the level of the calculated values of the induction of the static magnetic field of the project "Russian Maglev" there is a negative effect on the proliferative activity of the organotypic tissue culture of the cerebral cortex and spleen.
  2. The presented biological model of evaluation of the influence of static magnetic fields in the organotypic tissue culture allows to carry out preliminary testing of physical protection means intended for use in the project "Russian Maglev".

Artemy V. Rubinsky

Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation

Author for correspondence.
Email: rubinskiyav@1spbgmu.ru
ORCID iD: 0000-0003-1041-8745
SPIN-code: 3020-0781

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089

PhD

Timur D. Vlasov

Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation

Email: tvlasov@yandex.ru
ORCID iD: 0000-0002-6951-7599
SPIN-code: 8367-1246

Russian Federation, 6/8, Lva Tolstogo street, St. Petersburg, 197089

MD, PhD, Professor

Natalia I. Chalisova

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: ni_chalisova@mail.ru
SPIN-code: 2139-7608

Russian Federation, 6, Makarova street, St.Petersburg, 199034

DSc (Biol), PhD, Professor

  • Антонов Ю. Ф., Зайцев А.А. Магнитолевитационная транспортная технология / под ред. В.А. Гапановича – М.: Физматлит, 2014. [Antonov YuF, Zajcev AA. Magnetogravitational transport technology. Gapanovich VA, editor. Moskow: Physmathlit; 2014. (In Russ.)].
  • Чалисова Н.И., Лесняк В.В., Ноздрачёв А.Д. Протекторное влияние аминокислот и олигопептидов при сочетанном действии с цитостатиком в культуре лимфоидной ткани // Доклады РАН. – 2009. – Т. 424. – № 5. – C. 700–704. [Chalisova NI, Nozdrachev AD, Lesnyak VV. Protective effect of amino acids and oligopeptides in combination with a cytostatic agent on lymphoid tissue culture. Doklady RAN. 2009;424(5):700-704. (In Russ.)].
  • Вахитов Т.Я., Чалисова Н.И., Ситкин С.И., Салль Т.С., и др. Низкомолекулярные компоненты метаболома крови регулируют пролиферативную активность в клеточных и бактериальных культурах // Доклады Академии наук. – 2017. – T. 472. – № 4. – С. 491–493. [Vakhitov TY, Demyanova EV, Morugina AS, Petrov AV, Chalisova NI et al. Low-molecular-weight components of the metabolome control the proliferative activity in cellular and bacterial cultures. Doklady RAN. 2017;472(4):491-493. (In Russ.)].
  • Penniyainen VA, Chalisova NI, Nozdrachev AD. Interactions of cytokines and their components in nervous and lymphoid tissue cultures. Doklady Biological Sciences. 2002;384(1-6):199-201. doi: 10.1023/a:1016053021219.
  • Хавинсон В.Х., Морозов В.Г., Чалисова Н.И., Окулов В.Б. Влияние пептидов мозга на загущение нервной ткани в пробирке // Цитология. – 1997. – Т. 39, № 1. – C. 575–576. [Khavinson VKh, Morozov VG, Chalisova NI, Okulov VB. The effect of brain peptides on nerve tissue gells in vitro. Tsitologya. 1997;39(7):575-576. (In Russ.)].
  • Власов Т.Д., Рубинский А.В. Эксплуатация транспортной системы "Российский Маглев" и медикобиологические аспекты безопасности // Транспортные системы и технологии. – 2017. – № 3 (9). – С. 111-132. [Vlasov TD, Rubinskiy AV Operation of “russian maglev” transport system and medical-biological safety aspects. Transportation Systems and Technology. 2017;3(9):111-132. (In Russ., Engl.)]. doi: 10.17816/transsyst201733111-132.
  • Бреус Т.К., Бинги В.Н., Петрукович А.А.Магнитный фактор солнечно-земных связей и его влияние на человека: физические проблемы и перспективы // Успехи физических наук. – 2016. – Т. 186. – № 5. – С. 568-576. [Breus TK, Petrukovich AA, Binhi VN. Magnetic factor in solar-terrestrial relations and its impact on the human body: physical problems and prospects for research. Physics-Uspekhi. 2016;59(5):502–510. (In Russ.)]. doi: 10.3367/UFNr.2015.12.037693.
  • Чалисова, Н.И., Концевая Е.А., Войцеховская М.А., Комашня А.В. Регуляторное влияние кодируемых аминокислот на основные клеточные процессы у молодых и старых животных // Успехи геронтол. - 2011. - Т. 24, № 2. – с. 189-197. [Chalisova NI, Kontsevaya EA, Voytsehovskaya MA, Komashnya AV. The Regulatory Effects of Coded Amino Acids on Basic Cellular Processes in Young and Old Animals. Uspekhi Gerontologii. 2011;24(2):189-197. (In Russ.)] doi: 10.1134/s2079057012010067.
  • Schenck JF. Physical interactions of static magnetic fields with living tissues. Progress in Biophysics and Molecular Biology. 2005;87(2-3):185-204. doi: 10.1016/j.pbiomolbio.2004.08.009.
  • Villa M, Mustarelli P, Caprotti M. Minireview biological effects of magnetic fields. Life Sci. 1991;49(2):85-92. doi: 10.1016/0024-3205(91)90021-3.
  • Мамчик Н.П., Егорова A.M., Мокоян Б.О. Гигиенические особенности труда медицинского персонала, работающего с магнитно-резонансными томографами, с выявлением факторов риска // Системный анализ и управление в биомедицинских системах. – 2012. – Том 11. – №1. – С. 75-77. [Mamchik NP, Egorova AM, Mokoian BO. Hygienic estimation of working conditions at work with magnitno-resonant tomographs. System analysis and management in biomedical systems. 2012;11(1):75-77. (In Russ.)].
  • Binhi VN. Do naturally occurring magnetic nanoparticles in the human body mediate increased risk of childhood leukaemia with EMF exposure? International Journal of Radiation Biology. 2008;84(7):569-579. doi: 10.1080/09553000802195323.
  • Miyakoshi J. Effects of static magnetic fields at the cellular level. Progress in Biophysics and Molecular Biology. 2005;87(2-3):213-223. doi: 10.1016/j.pbiomolbio.2004.08.008.
  • Schreiber WG, Teichmann EM, Schiffer I, et al. Lack of mutagenic and co-mutagenic effects of magnetic fields during magnetic resonance imaging. Journal of Magnetic Resonance Imaging. 2001;14(6):779-788. doi: 10.1002/jmri.10010.
  • Khavinson VKh, Shataeva LK, Chernova AA. Effect of regulatory peptides on gene transcription. Bulletin of Experimental Biology and Medicine. 2003;136(3):288-290. doi: 10.1023/b:bebm.0000008986.02891.de.
  • Chalisova NI, Khavinson V, Nozdrachev AD. Modulating and protective effects of thymic peptides in lymphoid tissue culture. Doklady Biological Sciences. 2001;379(1/6):316-318. doi: 10.1023/a:1011683609587.
  • Yokus B, Cakir DU, Akdag MZ, et al. Oxidative DNA damage in rats exposed to extremely low frequency electromagnetic fields. Free Radical Research. 2005;39(3):317-323. doi: 10.1080/10715760500043603.
  • Saito K, Suzuki H, Suzuki K. Teratogenic effects of static magnetic field on mouse fetuses. Reproductive Toxicology. 2006;22(1):118-124. doi: 10.1016/j.reprotox.2005.08.003.
  • Robison JG, Pendleton AR, Monson KO et al. Decreased DNA repair rates and protection from heat induced apoptosis mediated by electromagnetic field exposure. Bioelectromagnetics. 2002;23(2):106-112. doi: 10.1002/bem.103.
  • Ghibelli L, Cerella C, Cordisco S, et al. NMR exposure sensitizes tumor cells to apoptosis. Apoptosis. 2006;11(3):359-365. doi: 10.1007/s10495-006-4001-1.
  • Hirai T, Yoneda Y. Transcriptional regulation of neuronal genes and its effect on neural functions: Gene expression in response to static magnetism in cultured rat hippocampal neurons. Journal of pharmacological sciences. 2005;98(3):219-224. doi: 10.1254/jphs.fmj05001x5.
  • Teodori L, Albertini MC, Uguccioni F et al. Static magnetic fields affect cell size, shape, orientation, and membrane surface of human glioblastoma cells, as demonstrated by electron, optic, and atomic force microscopy. Cytometry, Part A: The Journal of the Society for Analytical Cytology. 2005;69(2):75-85. doi: 10.1002/cyto.a.20208.
  • Fanelli C, Coppola S, Barone R et al. Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx. The FASEB Journal. 1999;13(1):95-102. doi: 10.1096/fasebj.13.1.95.
  • Jandová A, Mhamdi L, Nedbalová M et al. Effects of magnetic field 0.1 and 0.05 mT on leukocyte adherence inhibition. Electromagnetic Biology and Medicine. 2005;24(3):283-292. doi: 10.1080/15368370500379681.
  • Tokalov SV, Gutzeit HO. Weak electromagnetic fields (50 Hz) elicit a stress response in human cells. Environmental Research. 2004;94(2):145-151. doi: 10.1016/s0013-9351(03)00088-4.
  • Рубинский А.В., Носкин Л.А. Медико-биологические подходы к проблемам безопасной эксплуатации магнитолевитационного транспорта // Транспортные системы и технологии. – 2016. – T. 2. – No 4. – C. 114-127. Rubinskiy AV, Noskin LA. Biomedical aspects of problems safe usage of transport. Transportation Systems and Technology. 2016;2(4):114-127. (In Russ., Engl.)]. doi: 10.17816/transsyst201624114-127.

Supplementary files

Supplementary Files Action
1. Fig. The SMF influence on the cortex (1) and spleen (2) in isolation (dark bars) and in combination with Cortexin® and Timalin® respectively (light bars) View (64KB) Indexing metadata

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