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Vol. 24, Art. 37 (pp. 488-497)    |    2023       

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Evaluation of the immunobiological safety and integral haematological indices of a new pedifen pharmaceutical form

Stosman K.I.1,2, Kubarskaya L.G.1, Zolotoverkhaya E.A.1, Melikhova M.V.1

1 The Federal State-Financed Institution Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency
2 Smorodintsev Research Institute of Influenza, Russian Federation

Brief summary

Inhalation chemical injuries are a major cause of medical treatment in industrial accidents and man-made disasters. Pulmonotoxicant poisoning is manifested by damage to the respiratory tract, and can also lead to the development of toxic pulmonary edema. The search for new antidote therapy for this pathology is relevant. The aim is to study the effect of a new pharmaceutical form of Pedifen for the treatment of toxic pulmonary edema on immunological parameters and integral hematological indices. Materials and methods. The study was performed in 86 male CBA mice, 15 male guinea pigs, and 30 male outbred rats. The effect of Pedifen on delayed-type hypersensitivity reaction, of immunoglobulins G and M production, of peritoneal macrophages phagocytic activity were studied, and spleen and thymus weight and their organ to body weight ratio were determined. Allergenicity was assessed in mice and guinea pigs using delayed hypersensitivity reactions and the conjunctival tests. Integral hematological indices characterizing the immunoreactivity were calculated. Results. It was shown that inhalation of Pedifen to mice at a dose 3.4 mg/kg for 14 days did not affect the innate and adaptive immunity, the organ-to-body weight ratio of thymus and spleen. The dose of the drug, equal to 10.2 mg/kg, had a stimulating effect on the cells functional activity of the immune system. The total titer of antibodies, IgG titer, delayed hypersensitivity reaction index and phagocytic activity of peritoneal macrophages in mice from the experimental and the control group were significantly different. Hematological markers did not change after 14 days of the drug administration at doses of 2 mg/kg and 6 mg/kg to rats. Pedifen demonstrated no allergenic activity. Conclusion. Pedifen demonstrated no immunotoxicity and allergenicity. A threefold increase in the therapeutic dose resulted in immune stimulation of the cells functional activity of adaptive and innate immunity


Key words

toxic pulmonary edema; immunotoxicity; hypersensitivity reaction; hematological indices

Reference list

1.Belih V.G., Timoshevskii V.A. Mediko-sanitarnoe obespechenie naseleniya pri likvidacii posledstvii chrezvichainih sityacii himicheskoi prirodi: ychebno-metodicheskoe posobie dlya obychaushihsya po vsem napravleniyam visshego obrazovaniya. 2022. Available at: https://niioz.ru/upload/iblock/8da/8da587613c1db1e7b2af7ddec8a9887f.pdf


2. Kycenko S.A. Osnovi toksikologii. SPb.: Foliant, 2004. 720 s.


3. Nechiporenko S.P., Barinov V.A., Petrov A.N. Rol antidotov v lechenii ostrih otravlenii (proshloe i nastoyashee). Toksikologicheskii vestnik. 2011; 6(111): 38- 42.


4. Chepyr S.V., Udin M.A., Drachev I.S. i dr. Sindromoshodnie patologicheskie processi pri toksicheskih i radiacionnih porajeniyah: ocenka mehanizmov i poisk podhodov k farmakologicheskoi korrekcii. Voenno-medicinskii jyrnal. 2021; 342 (4): 26-30.


5. Flanagan R.J., Jones A.L. Antidotes. London & New York: Taylor and Francis, 2002. 317 p.


6. Lawrence D.T., Kirk M.A. Chemical terrorism attacks: update on antidotes. Emerg Med Clin N Am. 2007; 25: 567-595.


7. Grebenuk A.N., Minaev D.U. Sovremennoe sostoyanie antidotnoi terapii ostrih otravlenii himicheskoi etiologii v zarybejnih stranah. Voenno-medicinskii jyrnal. 2010; 331(1): 49-52.


8. Nazarov V.B., Gladkih V.D., Boyarincev V.V. i dr. Aktyalnie problemi formirovaniya rezervov sredstv antidotnoi terapii dlya likvidacii mediko-sanitarnih posledstvii chrezvichainih sityacii. Toksikologicheskii vestnik. 2011; 6(111): 33-37.


9. Szinicz L., Worek F., Thiermann H., et al. Development of antidotes: problems and strategies. Toxicology. 2007; 233: 23-30.


10. Mironov A.N., Bynatyan N.D. i dr. Rykovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Chast pervaya. M.: Grif i K. 2012. 944 s.


11. Chereshnev V.A., Shilov Y.I., Chereshneva M.V., et al. Effect of polyoxidonium on phagocytic cell function. Experimental and clinical estimation of potential inclusion of polyoxidonium in complex terpy in penetrating eye injury. Russian journal of Immunology. 2000; 5(1): 40-52.


12. Vladikin A.L. Rol holinergicheskoi i immynnoi sistem v regylyacii vospaleniya pri anafilakticheskom i endotoksicheskom shoke / avtoref. dis. k.b.n., SPb, 2009.


13. Parahonskii A.P., Egorova S.V. Holinergicheskie mehanizmi regylyacii immynnogo otveta. Sovremennie problemi nayki i obrazovaniya. 2008; 4. Available at: https://science-education.ru/ru/article/view?id=2859


14. Halder N., Lal G. Cholinergic system and its therapeutic importance in inflammation and autoimmunity. Frontiers in Immunology. 2021; 12: 660342 https://doi: 10.3389/fimmu.2021.660342


15. Shylepko M.A., Bichkov M.L., Kylbackii D.S., Lukmanova E.N. Nikotinovie acetilholinovie receptori cheloveka. Chast II: ne-neironalnaya holinergicheskaya sistema. Bioorganicheskaya himiya. 2019; 45(3): 227-237. https://doi: 10.1134/S0132342319020131


16. Papatriantafyllou M. Neuroimmunology: ChATty B cells. Nat Rev Immunol. 2013; 13(2): 70. https://doi: 10.1038/nri3396


17. Andersson U., Tracey K.J. Neural reflexes in inflammation and immunity. J Exp Med. 2012; 209: 1057-1068. https://doi: 10.1084/jem.20120571


18. Corradi J., Bouzat C. Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery. Mol. Pharmacol. 2016; 90: 288-299.


19. Nejinskaya G.I., Nazarov P.G., Evdokimova N.R., i dr. Holinergicheskaya regylyaciya anafilakticheskogo shoka: vliyanie C-reaktivnogo belka. Citokini i vospalenie. 2004; 3(1): 44-48.