Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model

Layilya Baktybayeva; Guldana Daulet; Alexey Zazybin; Valentina Yu; Yekaterina Ostapchuk; Yuliya Perfilyeva; Aikyn Kali; Nurshat Abdolla; Aigul Malmakova; Nuraly Baktybai; Zhanerke Temirbekova; Khadichahan Rafikova

doi:10.3390/molecules28031378

Molecules (Feb 2023)

Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model

Layilya Baktybayeva,
Guldana Daulet,
Alexey Zazybin,
Valentina Yu,
Yekaterina Ostapchuk,
Yuliya Perfilyeva,
Aikyn Kali,
Nurshat Abdolla,
Aigul Malmakova,
Nuraly Baktybai,
Zhanerke Temirbekova,
Khadichahan Rafikova

Affiliations

Layilya Baktybayeva: Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av., 71, Almaty 050040, Kazakhstan
Guldana Daulet: Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av., 71, Almaty 050040, Kazakhstan
Alexey Zazybin: School of Chemical Engineering, Kazakh British Technical University, Tole Bi Str., 59, Almaty 050000, Kazakhstan
Valentina Yu: Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, Walikhanov Str., 106, Almaty 050010, Kazakhstan
Yekaterina Ostapchuk: Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov Str., 86, Almaty 050012, Kazakhstan
Yuliya Perfilyeva: Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov Str., 86, Almaty 050012, Kazakhstan
Aikyn Kali: Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov Str., 86, Almaty 050012, Kazakhstan
Nurshat Abdolla: Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov Str., 86, Almaty 050012, Kazakhstan
Aigul Malmakova: Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, Walikhanov Str., 106, Almaty 050010, Kazakhstan
Nuraly Baktybai: Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av., 71, Almaty 050040, Kazakhstan
Zhanerke Temirbekova: Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av., 71, Almaty 050040, Kazakhstan
Khadichahan Rafikova: Department of Chemical and Biochemical Engineering, Institute of Oil and Gas Geology, Satbayev University, Almaty 050013, Kazakhstan

DOI: https://doi.org/10.3390/molecules28031378
Journal volume & issue: Vol. 28, no. 3
p. 1378

Abstract

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According to the WHO, the secondary form of hematopoietic-depressive status increases the risk of death in people with oncological, infectious, and hormonal diseases. The choice of drugs that stimulate the hematopoietic activity of B-lymphopoiesis is limited. The current leucopoiesis drugs have a number of side effects: thymic preparations stimulate the production of PGE2, which causes chronic inflammation and various autoimmune diseases through the differentiation of T helper 1 (Th1) cells, the proliferation of Th17 cells, and the production of IL-22 from Th22 cells through EP2 and EP4 receptors; cytokine preparations can cause uncontrolled immune reactions and impaired contractility of smooth and cardiac muscles; drugs based on nucleic acids can stimulate the division of all cells, including bacterial and cancerous ones. The use of oligonucleotides such as ribozymes and antisense oligodeoxynucleotides (AS-ODNs) shows promise as therapeutic moieties, but faces a number of challenges such as nuclease sensitivity, off-target effects, and efficient delivery. The search for substances that stimulate B-lymphopoiesis among ionic compounds was motivated by the discovery of the unique properties of lidocaine docusate, one of the first ionic liquid forms of the known drugs. The lidocaine docusate (protonated form of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide + docusate-anion (dioctylsulfosuccinate))) suppresses the division of pheochromocytoma cells and activates immunity in rats. The trimecaine-based ionic compound (TIC) demonstrates high B-lymphopoiesis-stimulating activity. The TIC compound stimulates an increase in the volume of transitional B cells, which play an important role for further differentiation and formation of a sufficient number of mature B1 cells and mature B2 cells, where mature B2 cells make up the bulk of the functional population of B lymphocytes. The TIC compound most strongly stimulated the restoration of the number of marginal zone B cells, follicular B cells, and activated germinal center B cells after the cytotoxic emptying of the follicular centers of the spleen induced cyclophosphamide. It significantly exceeds the activity of the comparison drug methyluracil. The TIC compound does not affect the level of pro-B, pre-B-I, or pre-B-II bone marrow cells, which prevents the risk of the formation of immature functionally defective cells.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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