聚乙二醇化透明质酸酶免疫毒性的研究

Q4 Biochemistry, Genetics and Molecular Biology Sibirskii nauchnyi meditsinskii zhurnal Pub Date : 2023-10-30 DOI:10.18699/ssmj20230512
K. I. Ershov, A. M. Shvetsova, E. Yu. Sherstoboev, A. A. Churin, V. V. Zhdanov, M. A. Korolev, P. G. Madonov
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引用次数: 0

摘要

安全药物的开发在医药工业中占有特殊的地位。其临床前阶段的主要任务之一是评估所开发药物对身体和各种系统(包括免疫系统)可能产生的毒性作用。本研究的目的是研究聚乙二醇透明质酸酶(PEG- HYAL)的免疫毒性。材料和方法。将F1(CBA/C57Bl/6)小鼠分为不同剂量(50、500、1250、2500、5000 U/kg)灌胃和腹腔注射PEG-HYAL的亚组。测定脾脏中抗体产生细胞的数量、中央和外周免疫器官的质量和细胞数量、腹腔巨噬细胞和中性粒细胞的吞噬活性、延迟性超敏反应(DHR)、绵羊红细胞血凝素水平、自发和丝裂原诱导的脾细胞增殖。结果。PEG-HYAL不诱导DHR,不抑制腹腔巨噬细胞的吞噬活性,50 ED/kg剂量对红细胞血凝素含量无显著影响,500 ED/kg剂量可显著降低特异性抗体滴度。当实验动物暴露于PEG-HYAL剂量为50和500 U/kg时,脾细胞自发增殖和丝裂原诱导的增殖减少。结论。PEG-HYAL试验产生的结果可用于证实基于PEG-HYAL的药物的施用。
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Study of the immunotoxic properties of pegylated hyaluronidase
The development of safe drugs occupies a special place in the pharmaceutical industry. One of the main tasks of its preclinical phase is to evaluate possible toxic effects of the developed drug on the body and on various systems, including the immune system. The aim of our work was to study immunotoxic properties of pegylated hyaluronidase (PEG- HYAL). Material and methods. Mice F1(CBA/C57Bl/6) were divided into subgroups which were intragastric and intraperitoneally administered with PEG-HYAL in different dosages (50, 500, 1250, 2500 and 5000 U/kg). The number of antibody-producing cells in the spleen, the mass and cellularity of central and peripheral immune organs, phagocytic activity of peritoneal macrophages and neutrophils, delayed hypersensitivity reaction (DHR), level of hemagglutinin to sheep erythrocytes, spontaneous and mitogen-induced splenocyte proliferation were determined. Results. PEG-HYAL did not induce DHR, did not suppress phagocyte activity of peritoneal macrophages, at a dose of 50 ED/kg did not significantly affect the hemagglutinin content to erythrocytes, but at a dose of 500 ED/kg did statistically significantly reduce the titer of specific antibodies. When experimental animals were exposed to PEG-HYAL at doses of 50 and 500 U/kg, spontaneous and mitogen-induced proliferation of splenocytes decreased. Conclusions. The PEG-HYAL trial produced results that can be used to substantiate the administration of the PEG-HYAL-based medication.
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来源期刊
CiteScore
0.40
自引率
0.00%
发文量
54
审稿时长
12 weeks
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