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Experimental study of acute toxicity of the intramuscular form of a specific immunobiostimulator — transfer factor

https://doi.org/10.32634/0869-8155-2024-386-9-40-47

Abstract

Relevance. The article presents data on the toxicological assessment of the safety of the specific immunobiostimulant of antigen-directed action “Transfer Factor” in a form ready for intramuscular administration and obtained from the blood of hyperimmunized donors on laboratory animals in an acute experiment.

Methods. The object of the study was the finished form of “Transfer Factor”, the acute toxicity of which was determined in models on laboratory animals (nonlinear mice, nonlinear rats).

Results. It was found that after administration of the drug to mice intramuscularly (0.25 ml/head) and intraperitoneally (0.5 ml/head), to rats intramuscularly (2.5 ml/head) and intraperitoneally (2.5 ml/head), muscle tremor is observed, disappearing after 15–20 minutes. Intraperitoneal administration of the drug to mice and rats in dosages of 0.75 ml/head and 3.75 ml/head, respectively, determines the presence of tremor lasting 40 minutes. During the 14-day observation period, the body weight of mice and rats increases by 10.15-14.25 and 11.84-17.67%. Autopsy of animals does not reveal visible changes in the location of organs and fluid in the abdominal and pleural cavities. However, some pathological changes in color, consistency and size are found in the lungs, heart, spleen and liver with intramuscular administration of Transfer Factor to mice and rats at a dose of 0.25 ml/head and 2.5 ml/head, intraperitoneal administration to mice at a dose of 0.5 ml/head and 0.75 ml/head and to rats 2.5 ml/head and 3.75 ml/head. Based on the totality of changes in the vital signs of laboratory animals, body weight and macroscopic characteristics of internal organs according to GOST 12.1.007-76, the drug “Transfer Factor” can be classified as hazard class IV “Low-hazard substances”.

About the Authors

P. V. Burkov
South Ural State Agrarian University
Russian Federation

Pavel Valerievich Burkov, Candidate of Veterinary Sciences, Head of the Research Center for Animal Reproduction Biotechnology

13 Gagarina Str., Troitsk, Chelyabinsk region, 457100



M. A. Derkho
South Ural State Agrarian University
Russian Federation

Marina Arkadyevna Derkho, Doctor of Biological Sciences, Head of the Department of Natural Sciences

13 Gagarina Str., Troitsk, Chelyabinsk region, 457100



M. B. Rebezov
Gorbatov Research center for Food Systems; Ural State Agrarian University
Russian Federation

Maksim Borisovich Rebezov, Doctor of Agricultural Sciences, Candidate of Veterinary Sciences, Professor, Chief Researcher; Doctor of Agricultural Sciences, Candidate of Veterinary Sciences, Professor of the Department of Biotechnology and Food Products

26 Talalikhin Str., Moscow, 109316

42 Karl Liebknecht Str., Yekaterinburg, 620075



P. N. Shcherbakov
South Ural State Agrarian University
Russian Federation

Pavel Nikolaevich Shcherbakov, Doctor of Veterinary Sciences, Professor of the Department of Infectious Diseases and Veterinary and Sanitary Expertise

13 Gagarina Str., Troitsk, Chelyabinsk region, 457100



A. O. Derkho
South Ural State Agrarian University
Russian Federation

Arina Olegovna Derkho, Graduate student

13 Gagarina Str., Troitsk, Chelyabinsk region, 457100



References

1. Islamiati Yu. et al. The Potential of Antivirus Compounds in Gletang (Tridax procumbens Linn.) in Inhibiting 3CLpro Receptor of SARS-CoV-2 Virus by In Silico. Pharmacognosy Journal. 2022; 14(6): 796-805. https://doi.org/10.5530/pj.2022.14.170

2. Kharisma V.D. et al. Garcinoxanthones from Garcinia mangostana L. against SARS-CoV-2 infection and cytokine storm pathway inhibition: A viroinformatics study. Journal of Pharmacy and Pharmacognosy Research. 2023; 11(5): 743–756. https://doi.org/10.56499/jppres23.1650_11.5.743

3. Rahman A.T. et al. In Silico Study of the Potential of Endemic Sumatra Wild Turmeric Rhizomes (Curcuma Sumatrana: Zingiberaceae) As Anti-Cancer. Pharmacognosy Journal. 2023; 14(6): 806–812. https://doi.org/10.5530/pj.2022.14.171

4. Kuzmin I.A., Bobkova E.V., Alsynbayеv M.M. Transfer factor: properties and mechanisms of action. Bashkortostan medical journal. 2009; 4(3): 71–74 (in Russian). https://elibrary.ru/kvtfgn

5. Fu W. et al. CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nature Communications. 2019; 10: 4355. https://doi.org/10.1038/s41467-019-12321-3

6. Malyuk M.О., Yehorov O.V., Kharkevych I.O., Klymchuk V.V., Savchuk T.L. The content of leukocytes in the blood of recipient rabbits after allogeneic transfusion of packed red blood cells. Regulatory Mechanisms in Biosystems. 2024; 15(1): 37–41. https://doi.org/10.15421/022405

7. Szczotka M., Kuźmak Ja. Cytokine secretion in stem cells of cattle infected with bovine leukaemia virus. Journal of Veterinary Research (Poland). 2024; 68(1): 19–33. https://doi.org/10.2478/jvetres-2024-0012

8. Burkat N.V., Popova N.Yu., Isaeva A.G., Krivonogova A.S. Leukocyte indexes for equine immune status assessment. International Scientific and Practical Conference “From Modernization to Rapid Development: Ensuring Competitiveness and Scientific Leadership of the Agro-Industrial Complex” (IDSISA 2024). Les Ulis, 2024; 23005. https://doi.org/10.1051/bioconf/202410823005

9. Wang J.F., Park A.J., Rendini T., Levis W.R. Lawrence Transfer Factor: Transference of Specific Immune Memory by Dialyzable Leukocyte Extract from a CD8+ T Cell Line. Journal of Drugs in Dermatology. 2017; 16(12): 1198–1206.

10. Castrejón Vázquez M.I. et al. Dialyzable Leukocyte Extract (Transferon™) Administration in Sepsis: Experience from a Single Referral Pediatric Intensive Care Unit. BioMed Research International. 2019: 8980506. https://doi.org/10.1155/2019/8980506

11. Macias A.E., Guaní-Guerra E. “Transfer Factor”: Myths and Facts. Archives of Medical Research. 2020; 51(7): 613–622. https://doi.org/10.1016/j.arcmed.2020.06.016

12. Zajícová A., Javorková E., Trošan P., Chudíčková M., Krulová M., Holáň V. A Low-Molecular-Weight Dialysable Leukocyte Extract Selectively Enhances Development of CD4⁺RORγt⁺ T Cells and IL-17 Production. Folia Biologica. 2014; 60(6): 253–260. https://doi.org/10.14712/fb2014060060253

13. Ojeda M.O., Veer C.v., Fernández Ortega C.B., Rosainz M.d.J. Araña, Buurman W.A. Dialyzable Leukocyte Extract differentially regulates the production of TNFα, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells. Inflammation Research. 2005; 54(2): 74–81. https://doi.org/10.1007/s00011-004-1326-5

14. Franco-Molina M.A. et al. Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide production in lipopolysaccharide-stimulated human blood cells. Cytotherapy. 2007; 9(4): 379–385. https://doi.org/10.1080/14653240701320262

15. Hromas J., Vacek A., Hofer M., Lukšíková E., Svoboda J., Schneiderová H. Hemopoiesis-Stimulating Effects and Enhanced Survival of Irradiated Mice after Peroral or Intraperitoneal Administration of Ultrafiltered Pig Leukocyte Extract (UPLE, IMUNOR®). Immunopharmacology and Immunotoxicology. 2002; 24(4): 651–664. https://doi.org/10.1081/iph-120016049

16. Vacek A., Hofer M., Schneiderová H., Svoboda J. Ultrafiltered Pig Leukocyte Extract (UPLE, IMUNOR®) Potentiates Hematopoiesis–Stimulating Effects of G-CSF In Vitro and Improves the Outcome of Treatment of Hematopoietic Radiation Damage in Mice with G-CSF. Immunopharmacology and Immunotoxicology. 2005; 27(4): 647–659. https://doi.org/10.1080/08923970500494001

17. Yimam M. et al. Discovery of Transfer Factors in Plant-Derived Proteins and an In Vitro Assessment of Their Immunological Activities. Molecules. 2023; 28(24): 7961. https://doi.org/10.3390/molecules28247961

18. Qin H. et al. Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design. Journal for ImmunoTherapy of Cancer. 2021; 9(9): e003149. https://doi.org/10.1136/jitc-2021-003149

19. Stosman K., Sivak K., Aleksandrov A., Buzitskaya Z., Rassokha T., Stukova M. Preclinical Safety Evaluation: Acute and Repeated-Dose Toxicity of a New Intranasal Recombinant Vector Vaccine TB/FLU-04L Against Tuberculosis. Drug Research. 2022; 72(4): 215–219. https://doi.org/10.1055/a-1771-5985

20. Badrick T., Bowling F. Clinical utility — information about the usefulness of tests. Clinical Biochemistry. 2023; 121–122: 110656. https://doi.org/10.1016/j.clinbiochem.2023.110656

21. Hauser R.G., Quine D.B., Iscoe M., Arvisais-Anhalt S. Development and implementation of a standard format for clinical laboratory test results. American Journal of Clinical Pathology. 2022; 158(3): 409–415. https://doi.org/10.1093/ajcp/aqac067

22. Stanimirov B., Sekeruš V., Đanić M., Pavlović N., Mikov M., Stankov K., Katanić Ja. Drug interference with biochemical laboratory tests. Biochemia Medica. 2023; 33(2): 123–131. https://doi.org/10.11613/bm.2023.020601

23. Kalinina A. et al. Safety evaluation of the mouse TCRα — transduced T cell product in preclinical models in vivo and in vitro. Biomedicine & Pharmacotherapy. 2022; 145: 112480. https://doi.org/10.1016/j.biopha.2021.112480

24. Burkov P.V., Shcherbakov P.N., Rebezov M.B. Vaccinal prevention of lumpy skin disease in Black-and-White cows and increasing its effectiveness using a transfer factor. Agrarian science. 2022; (4): 11–15 (in Russian). https://doi.org/10.32634/0869-8155-2022-358-4-11-15

25. Akhmadiev P.A., Khismatullina Z.R., Iskhakov E.R. Orientational habits in new spatial environmental conditions during oral administration of the “Transfer factor” in rats. Journal of Volgograd state medical university. 2023; 20(2): 153–156 (in Russian). https://doi.org//10.19163/1994-9480-2023-20-2-153-156

26. Сhizhov A.Y., Kirkutis A., Andruskiene J. Perspectives in the Application of Immunocorrector — “Transfer factorTM” in Immunoprophylaxis Programmes and Immunorehabilitation. Reabilitacijos mokslai: slauga, kineziterapija, ergoterapija. 2016; 15(2): 5–17. https://doi.org/10.33607/rmske.v2i15.703

27. Tretiakov A.V., Markov V.F., Yaroshuk S.B., Kovalev I.S. Study of the target efficiency and toxicity of the insecticide with new preparative form. AIP Conference Proceedings. 4th International Conference on Modern Synthetic Methodologies for Creating Drugs and Functional Materials, MOSM 2020. American Institute of Physics Inc. 2021; 030044. https://doi.org/10.1063/5.0068399

28. Vikhrova S.V., Rutenberg O.L., Smirnov A.V., Petukhov A.E., Barinskaya T.O. Improvement of methods and means of measuring the content of toxicants in biological objects. Journal of Physics: Conference Series. V International Scientific and Technical Conference “Metrology of Physical and Chemical Measurements, MPM 2021”. 2022; 012013. https://doi.org/10.1088/1742-6596/2192/1/012013

29. Burkov P.V., Derkho M.A., Rebezov M.B., Shcherbakov P.N., Derkho A.O., Stepanova K.V. Immunological status of sows during the reproductive cycle and correction of its condition with an antigen-directed biostimulator. Agrarian science. 2023; (12): 58–66 (in Russian). https://doi.org/10.32634/0869-8155-2023-377-12-58-66

30. Burkov P.V. et al. Pathological features of the lungs and liver of piglets under conditions of constant vaccination of livestock against circovirus infection. Theory and practice of meat processing. 2023; 8(1): 4–11. https://doi.org/10.21323/2414-438X-2023-8-1-4-11

31. Burkov P.V., Derkho M.A., Rebezov M.B., Shcherbakov P.N. Circovirus as a factor controlling the effectiveness of pregnancy in sows. Agrarian science. 2023; (8): 27–35 (in Russian). https://doi.org/10.32634/0869-8155-2023-373-8-27-35

32. Burkov P.V., Rebezov M.B., Derkho M.A., Shcherbakov P.N., Derkho A.O. Immunometabolic features of the formation of post-vaccination immunity against porcine circovirus type 2 in sows. Agrarian science. 2024; (7): 38–48 (in Russian). https://doi.org/10.32634/0869-8155-2024-384-7-38-48

33. Titov E.A., Sosedova L.M., Novikov M.A., Zvereva M.V., Rukavishnikov V.S., Lakhman O.L. The Analysis of Acute and Subacute Toxicity of Silver Selenide Nanoparticles Encapsulated in Arabinogalactan Polymer Matrix. Polymers. 2022; 14(15): 3200. https://doi.org/10.3390/polym14153200

34. Koterov A.N., Ushenkova L.N., Zubenkova E.S., Vaynson A.A., Biryukov A.P., Samoylov A.S. Dependence of Body Weight on Age for Random-Bred Albino Rat and for Eight Lines of Laboratory Rat: Synthetic Studies of Data from Experimental Works and Nurseries in Aspect of the Relationship with Radiosensitivity. Some Characteristics of Rat Species. Medical Radiology and radiation safety. 2018; 63(2): 15–17 (in Russian). https://doi.org/10.12737/article_5ac6190e95da25.42157674

35. Ghiciuc C.M., Shleghm M.R., Vasile C., Tantaru G., Creteanu A., Ochiuz L. Study on Acute Toxicity of Amiodarone New Complexes with Cyclodextrin. Frontiers in Pharmacology. 2021; 12: 640705. https://doi.org/10.3389/fphar.2021.640705

36. Sysoev Yu.I. et al. Pharmaco-encephalographic assessment of the dose dependence of antipsychotic drug effects in rats. I.M. Sechenov Russian Journal of Physiology. 2023; 109(11): 1665–1683 (in Russian). https://doi.org/10.31857/S0869813923110110

37. Combs M.D., Hamlin A., Quinn J.C. A single exposure to the tremorgenic mycotoxin lolitrem B inhibits voluntary motor activity and spatial orientation but not spatial learning or memory in mice. Toxicon. 2019; 168: 58–66. https://doi.org/10.1016/j.toxicon.2019.06.228

38. Hamm J. et al. Performance of the GHS Mixtures Equation for Predicting Acute Oral Toxicity. Regulatory Toxicology and Pharmacology. 2021; 125: 105007. https://doi.org/10.1016/j.yrtph.2021.105007

39. Zobnin Yu.V. Acute toxic neuropathies. Siberian Medical Journal. 2008; 79(4): 106–110 (in Russian). https://elibrary.ru/jwkqbb

40. Ahloy-Dallaire J., Klein J.D., Davis J.K., Garner J.P. Automated monitoring of mouse feeding and body weight for continuous health assessment. Laboratory Animals. 2019; 53(4): 342–351. https://doi.org/10.1177/0023677218797974

41. Ong Y.S. et al. Acute and subacute toxicity profiles of thymoquinoneloaded nanostructured lipid carrier in BALB/c mice. International Journal of Nanomedicine. 2016; 11: 5905–5915. https://doi.org/10.2147/IJN.S114205

42. Bazikov I.A. et al. Macroscopic changes of the organs with the application of a niosomal form of antitumor medicine in experiment. Medical news of the North Caucasus. 2022; 17(1): 60–63 (in Russian). https://doi.org/10.14300/mnnc.2022.17016


Review

For citations:


Burkov P.V., Derkho M.A., Rebezov M.B., Shcherbakov P.N., Derkho A.O. Experimental study of acute toxicity of the intramuscular form of a specific immunobiostimulator — transfer factor. Agrarian science. 2024;1(9):40-47. (In Russ.) https://doi.org/10.32634/0869-8155-2024-386-9-40-47

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