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Abstract
Aim. To evaluate the antitumor effect of manganese, copper, and zinc gluconates in a model of myeloma Sp2/0-Ag14 in BALB/c strain mice.
Materials and methods. BALB/c mice with transplanted Sp2/0-Ag14 myeloma received orally for three weeks manganese, copper and zinc gluconates synthesized at the Ufa Institute of Chemistry, Ufa Research Center, Russian Academy of Sciences; the reference drug was cyclophosphamide. On day 22, organs and tumor masses were histologically examined, and the antitumor effect was assessed by calculating tumor regression rates: body weight gain inhibition (WGI), ascites growth inhibition (AGI) and after 3 months - an increase in life expectancy (ILE).
Results. Histological tests showed the absence of solid tumor in the groups of mice that underwent three weeks of treatment with metal gluconates. No significant changes were found in organ tissues compared to the control group of intact animals. In the group of untreated animals, the formation of a nodular tumor with a developed vascular network was registered. After cyclophosphamide therapy there was detected venous stasis, leading to the accumulation of lymphoid cells in the walls of the tumor cells. WGI, AGI, and ILE in the group with the reference drug cyclophosphamide were 28.8 %, 29.4 %, and 153.5 % respectively, that was close to the values of the group with copper gluconate therapy. Manganese and zinc gluconates showed higher efficiency, exceeding the effectiveness of the reference drug by 30-40 %.
Conclusion. Administration of manganese, copper and zinc gluconates for three weeks slows down the development of the tumor process in BALB/c mice with Sp2/0-Ag14 myeloma: no solid tumor was detected at sampling; tumor growth was noted only after the drugs were discontinued. To support the results of the experiment morphological control and statistical calculations using the Statistica 10.0 program were applied. Inhibition of tumor growth (30-40 %) was recorded by changes in body weight, ascites accumulation and the increase in life expectancy.
References
Esfahani K., Roudaia L., Buhlaiga N., et al. A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol. 2020; 27(2): 87-97.-DOI: https://doi.org/10.3747/co.27.5223.
Гук Д.А., Красновская О.О., Белоглазкина Е.К. Координационные соединения биогенных металлов как цитотоксические агенты для терапии злокачественных новообразований. Успехи химии. 2021; 90(12): 1566-1623.-DOI: https://doi.org/10.1070/RCR5016. [Guk D.A., Krasnovskaya O.O., Beloglazkina E.K. Coordination compounds of biogenic metals as cytotoxic agents for the treatment of malignant neoplasms. Uspekhi Khimii = Russian Chemical Reviews. 2021; 90(12): 1566-1623.-DOI: https://doi.org/10.1070/RCR5016. (In Rus)].
Wang C., Zhang R., Wei X., et al. Metalloimmunology: The metal ion-controlled immunity. Adv Immunol. 2020; 145: 187-241.-DOI: https://doi.org/ 10.1016/bs.ai.2019.11.007.
Конкина И.Г., Иванов С.П., Князева О.А., и др. Физико-химические свойства и фармакологическая активность глюконатов Mn(II), Fe(II), Co(II), Cu(II) и Zn(II). Химико-фармацевтический журнал. 2002; 1: 18-25.-DOI: https://doi.org/10.1023/A:1015792623287. [Konkina I.G., Ivanov S.P., Knyazeva O.A., et al. Physico-chemical properties and pharmacological activity of gluconates Mn(II), Fe(II), Co(II), Cu(II) and Zn(II). Himiko-farmacevticheskyj zhurnal = Pharmaceutical Chemistry Journal. 2002; 1: 18-25.-DOI: https://doi.org/10.1023/A:1015792623287. (In Rus)].
Toren A., Yalon M., Dafni A., et al. Hgg-04. zinc enhances temozolomide cytotoxicity in pediatric glioblastoma multiforme model system. Neuro-Oncol. 2020; 22: 344-345.-DOI: https://doi.org/10.1093/neuonc/noaa222.295.
Du W., Gu M., Hu M., et al. Lysosomal Zn2+ release triggers rapid, mitochondria-mediated, non-apoptotic cell death in metastatic melanoma. Cell Rep. 2021; 3: 109848.-DOI: https://doi.org/ 10.1016/j.cellrep.2021.109848.
Costello L.C., Franklin R.B. Zinc: The wonder drug for the treatment of carcinomas. Acta Sci Cancer Biol. 2020; 4(5): 33-39.-DOI: https://doi.org/10.31080/ascb.2020.04.0223.
Lv M., Chen M., Zhang R., et al. Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res. 2020; 30: 966-979.-DOI: https://doi.org/10.1038/s41422-020-00395-4.
Ji P., Wang P., Chen H., et al. Potential of copper and copper compounds for anticancer applications. Pharmaceuticals. 2023; 16(2): 234.-DOI: https://doi.org/10.3390/ph16020234.
Князева О.А., Уразаева С.И., Конкина И.Г., и др. Антииммуносупрессивное действие глюконатов 3d-металлов при экспериментальном иммунодефиците. Казанский медицинский журнал. 2018; 2: 255-259.-DOI: https://doi.org/10.17816/KMJ2018-255. [Knyazeva O.A., Urazaeva S.I., Konkina I.G., et al. Antiimmunosuppressive action of 3d-metal gluconates in experimental immunodeficiency. Kazanskyj medicinskyj zhurnal = Kazan Medical Journal. 2018; 2: 255-259.-DOI: https://doi.org/10.17816/KMJ2018-255. (In Rus)].
Князева О.А., Уразаева С.И., Конкина И.Г. Глюконаты 3d-металлов: влияние на окислительный ииммунный гомеостаз, использование в терапии иммунодефицита. Москва: Издательский дом Академии Естествознания. 2021; 122 с.-DOI: https://doi.org/10.17513/np.448, ISBN: 978-5-91327-676-6. [Knyazeva O.A., Urazaeva S.I., Konkina I.G. 3d-metalgluconates: effect on oxidative and immunehomeostasis, useinimmunodeficiency therapy. Moscow: Publishing House of the Academy of Natural Sciences. 2021; 122.-DOI: https://doi.org/10.17513/np.448, ISBN: 978-5-91327-676-6. (In Rus)].
Князева О.А., Киреева Е.А., Конкина И.Г., и др. Влияние глюконатов 3d-металлов на лейкоцитарные показатели эндогенной интоксикации. Казанский медицинский журнал. 2022; 103(3): 427-433.-DOI: https://doi.org/10.17816/KMJ2022-427. [Knyazeva O.A., Kireeva E.A., Konkina I.G., et al. Effect of 3D metal gluconates on leukocyte indices of endogenous intoxication. Kazanskyj medicinskyj zhurnal = Kazan Medical Journal. 2022; 103(3): 427-433.-DOI: https://doi.org/10.17816/KMJ2022-427. (In Rus)].
Mycielska M.E., Mohr M.T.J., Schmidt K., et al. Potential use of gluconate in cancer therapy. Front Oncol. 2019; 9: 522-529.-DOI: https://doi.org/10.3389/fonc.2019.00522.
Jocelyn H., Bruce-Gregorios. Histopathologic Techniques. Dr. Joy Bruce. 2018; 789. ISBN: 0692183418, 9780692183410.
Волкова О.В., Елецкий Ю.К. Основы гистологии с гистологической техникой. Москва: Медицина. 1982: 304. [Volkova O.V., Eleckyj Yu.K. Basics of histology with histological technique. Moskow: Medicine. 1982: 304. (In Rus)].
Саркисов Д.С., Пальцев М.А., Хитров Н.К. Общая патология человека. 2-е издание, переработанная и дополненная. Москва: Медицина. 1997: 608. [Sarkisov D.S., Pal’cev M.A., Hitrov N.K. General human pathology. 2nd edition, revised and expanded. Moskow: Medicine. 1997: 608. (In Rus)].
Трещалина Е.М., Жукова О.С., Герасимова Г.К., и др. Методические указания по изучению противоопухолевой активности фармакологических веществ. Под ред. Р.У. Хабриева. Москва: Медицина. 2005: 637-651. [Treschalina E.M., Zhukova O.S., Gerasimova G.K., et al. Methodical instructions for the study of antitumor activity of pharmacological substances. Ed. RU. Khabrieva. Moskow: Medicine. 2005: 637-651. (In Rus)].
Fridman W.H., Pages F., Sautes-Fridman C., Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012; 12: 298-306.-DOI: https://doi.org/10.1038/nrc3245.
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