Original Empirical Research Protective Effects of Succinic Acid upon Exposure to the Low-Frequency Alternating Magnetic Field Determined in the Experiment

Introduction. The need to simulate the oxidative stress by an experiment of exposure to the low-frequency alternating magnetic field is induced by the persistent increase of the electromagnetic load on the endothermic organisms caused by the annual deterioration of the electromagnetic state of the environment. The low-frequency alternating magnetic field starts a chain of biochemical reactions in the laboratory animals, which alter the homeostasis against the increased intensity of free-radical oxidation (peroxidation) of biomembrane lipids. The preparations containing succinic acid have the antioxidant, antihypoxant, actoprotective and stress-protective effects, tested through various kind of modelling, however, the absence of data on the efficacy of succinic acid under the exposure to the alternating magnetic field has become the reason for the present experiment. The aim of the research is to determine the protective effects of succinic acid upon exposure of the laboratory rats to the low-frequency alternating magnetic field.

Materials and Methods. The objects of the research were 90 white outbred male rats weighing 200–250 g, divided into three groups: group 1 — intact, the animals were in standard vivarium conditions and were not exposed to any effect; group 2 — control, the rats were exposed to the low frequency alternating magnetic field (LF-AMF) for 21 days daily per 3 hours, preceded by daily intraperitoneal administration to animals of the 0.9% sodium chloride solution at a dose of 1 ml / kg straight before them being exposed to LF-AMF; group 3 — experimental, the rats were daily intraperitoneally administered the succinic acid at a dose of 100 mg / kg (1 ml / kg) for 21 days prior to being exposed to LF-AMF. The exposure to the low-frequency alternating magnetic field was created by the Helmholtz coils (of diameter 1 m) powered by the alternating current source with a frequency of 50 Hz, with a magnetic field induction of 0.4 mT, whereas the cages with animals were placed in the centre of the device. The actoprotective effect of succinic acid was checked on the 7th, 14th and 21st days from the beginning of the experiment by duration of swimming of rats in water. The antioxidant effect — by concentration of diene conjugates, lipid hydroperoxides, malondialdehyde, ceruloplasmin, vitamin E in the blood plasma of rats measured according to the commonly accepted methods. The stress-protective effect was determined by the masses of the adrenal glands, thymus gland, spleen and the number of erosive defects on the suRussian Federationace of the gastric mucosa.

Results. The experimental data has confirmed the actoprotective effect of succinic acid — the duration of swimming of the rats in the experimental group increased by 25–37% compared to the control one. The antioxidant effect of succinic acid under magnetic induction has been manifested in a decreased concentration of lipid peroxidation products against increased level of ceruloplasmin in the blood of rats in the experimental group compared to the animals in the control group. Administration of the succinic acid into the peritoneum of rats in the experimental group under exposure to the low frequency alternating magnetic field has prevented involution of the thymus gland by 45% (7th day), 56% (14th day), 71% (21th day) and the spleen by 52%, 58% and 66% respectively, alongside, the number of erosive and ulcerative defects on the suRussian Federationace of the gastric mucosa has decreased by 2.5–4 times compared to the animals in the control group.

Discussion and Conclusion. The protective effects of succinic acid upon exposure to the low-frequency alternating magnetic field have been confirmed that include the stress-protective, actoprotective and antioxidant effects of the exogenous succinate. The ability of succinic acid to prevent the negative changes in the internal organs caused by the magnetic loads is proved by the statistically significant excess of the mass coefficients of the thymus gland and spleen in the experimental group, compared to the control one, along with the fewer erosive defects on the suRussian Federationace of the gastric mucosa. Succinic acid reduces the intensity of lipid peroxidation processes upon the magnetic exposure due to reducing the concentration of lipid peroxidation products and increasing the level of ceruloplasmin in the blood of animals.

1. Kosolapov VA, Tregubova IA. Modeling Stress in an Experiment. Lekarstvennyi vestnik. 2022;23(2):17–19. (In Russ.).

2. Petrenev D.R. Reactions Peritoneal Macrophages of Rats on Prolonged Exposure to an Alternating Magnetic Field of Low Frequency 50 Hz. Francisk Skorina Gomel State University Proceedings. 2015;(93(6)):147–149. (In Russ.).

3. Rapiev RA, Mannapova RT. The Biochemical Status of the Animal Body as Compensatory-Regulatory Response, Amid the Stress. Fundamental Research. Biological Sciences. 2013;(10–12):2663–2666. (In Russ.).

4. Shiryaeva NV, Vaido AI, Shchegolev BF. The Influence of Non-Ionizing Electromagnetic Radiation on the Orientation-Exploratory Activity and Emotionality of Rats with Different Excitability of the Nervous System. In: Proceedings of the Republican Conference with International Participation, Dedicated to the 110th Anniversary of the Birth of V. A. Bandarin. “Physico-Chemical Biology as the Basis of Modern Medicine”. Minsk, May 24, 2019. Minsk: Belarusian State Medical University Publishing House; 2019. P. 148–150. (In Russ.).

5. Karthick T, Sengottuvelu S, Haja Sherief S, Duraisami. A Review: Biological Effects of Magnetic Fields on Rodents. Scholars Journal of Applied Medical Sciences (SJAMS). 2017;5(4E):1569–1580. URL: https://www.saspublishers.com/media/articles/SJAMS_54E1569-1580.pdf (accessed: 01.05.2024).

6. Anenberg S, Haines S, Wang E. Synergistic Health Effects of Air Pollution, Temperature, and Pollen Exposure: A Systematic Review of Epidemiological Evidence. Environmental health. 2020;1(19):130. https://doi.org/10.1186/s12940-020-00681-z

7. Lashin AP, Simonova NV, Simonova NP. Phytoprophylaxis of Dyspepsia in Newborn Calves. Bulletin of KrasGAU. 2015;(9(108)):189–192. (In Russ.).

8. Pirotta E, Thomas L, Costa DP, Hall AJ, Harris CM, Harwood J, et al. Understanding the Combined Effects of Multiple Stressors: A New Perspective on a Longstanding Challenge. Science of the Total Environment. 2022;821:153322. https://doi.org/10.1016/j.scitotenv.2022.153322

9. Lashin AP, Simonova NV. Phytopreparation in Correction of Oxidative Stress in Calves. Far Eastern Agraricultural Journal. 2017;(4(44)):131–135. (In Russ.).

10. Adjirackor NA, Harvey KE, Harvey SC. Eukaryotic Response to Hypothermia in Relation to Integrated Stress Responses. Cell Stress and Chaperones. 2020;25(6):833–846. https://doi.org/10.1007/s12192-020-01135-8

11. Ganapolsky VP, Agafonov PV, Matytsyn VO. Modeling of Cold-Stress Disadaptation in Rats to Develop Methods for Its Pharmacological Correction. Russian Biomedical Research. 2022;7(1):3–15. https://doi.org/10.56871/2489.2022.64.64.001 (In Russ.).

12. Cerri M, Mastrotto M, Tupone D, Martelli D, Luppi M, Perez E, et al. The Inhibition of Neurons in the Central Nervous Pathways for Thermoregulatory Cold Defense Induces a Suspended Animation State in the Rat. The Journal of Neuroscience. 2013;33(7):2984–2993. https://doi.org/10.1523/JNEUROSCI.3596-12.2013

13. Dorovskikh VA, Lee ON, Simonova NV. Remaxol in the Correction of Lipid Peroxidation Processes in Biomembranes Induced by Cold Exposure. Yakut Medical Journal. 2015;(4(52)):21–24. (In Russ.).

14. Lee TK, Kim DW, Sim H, Lee JC, Kim HI, Shin MC, et al. Hyperthermia Accelerates Neuronal Loss Differently between the Hippocampal CA1 and CA2/3 through Different HIF-1α Expression after Transient Ischemia in Gerbils. International Journal of Molecular Medicine. 2022;49(4):55. https://doi.org/10.3892/ijmm.2022.5111

15. Foster J, Hodder SG, Lloyd AB, Havenith G. Individual Responses to Heat Stress: Implications for Hyperthermia and Physical Work Capacity. Frontiers in Physiology. 2020;11:541483. https://doi.org/10.3389/fphys.2020.541483

16. Prikhodko VA, Selizarova NO, Okovity SV. Molecular Mechanisms for Hypoxia Development and Adaptation to It. Part I. Archiv patologii. 2021;83(2):52–61. https://doi.org/10.17116/patol20218302152 (In Russ.).

17. Prikhodko VA, Selizarova NO, Okovity SV. Molecular Mechanisms of Hypoxia Development and Adaptation to It. Part II. Archiv patologii. 2021;83(3):62–69. https://doi.org/10.17116/patol20218303162 (In Russ.).

18. Cerri M. The Central Control of Energy Expenditure: Exploiting Torpor for Medical Applications. Annual Review of Physiology. 2017;79:167–186. https://doi.org/10.1146/annurev-physiol-022516-034133

19. Deev RV, Bilyalov AI, Zhampeisov TM. Modern Ideas about Cell Death. Genes and Cells. 2018; 13(1):6–19. https://doi.org/10.23868/201805001

20. Semenza GL. Pharmacologic Targeting of Hypoxia-Inducible Factors. Annual Review of Pharmacology and Toxicology. 2019;59:379–403. https://doi.org/10.1146/annurev-pharmtox-010818-021637

21. Stalnaya ID. Method for Determining the Diene Conjugation of Unsaturated Higher Fatty Acids. In book: Modern Methods in Biochemistry. Moscow: Meditsina Publishing House; 1977. P. 63–64. (In Russ.).

22. Romanova LA, Stalnaya ID. Method for Determining the Lipid Hydroperoxides Using Ammonium Thiocyanate. In book: Modern Methods in Biochemistry. Moscow: Meditsina Publishing House; 1977. P. 64–65. (In Russ.).

23. Stalnaya ID, Garishvili TG. Method for Determining the Malonic Dialdehyde Using Thiobarbituric Acid. In book: Modern Methods in Biochemistry. Moscow: Meditsina Publishing House; 1977. P. 66−68. (In Russ.).

24. Колб В.Г., Камышников В.С. Клиническая биохимия. Минск: Беларусь; 1976. 311 с. Kolb VG, Kamyshnikov VS. Clinical biochemistry. Minsk: Belarus'; 1976. 311 p. (In Russ.).

25. Kisilevich RZh, Skvarko SI. Determination of Vitamin E in Blood Serum. Laboratornoe delo. 1977;(8):473–475. (In Russ.).