EFFICACY OF GRANULOCYTE COLONY-STIMULATING FACTOR AND ENTEROSORPTION IN MELPHALAN-INDUCED BONE MARROW SUPPRESSION IN GUERIN CARCINOMA GRAFTED RATS

O. Shevchuk, I. M. Todor, N. Lukianova, N. Rodionova, V. Nikolaev, V. Chekhun
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Abstract

Background. Side effects of antineoplastic agents (especially leukopenia and neutropenia) could be the main limiting factors for efficient treatment. Objective. The research is aimed at the study of myeloprotective capability of biosimilars of granulocyte colony stimulating factor (G-CSF) and granular carbon oral adsorbent C2 in melphalan-induced bone marrow suppression in Guerin carcinoma-grafted rats. Methods. Melphalan at the dose of 5.5 mg/kg was used to promote bone marrow suppression in the Guerin carcinoma grafted rats. To fight myelosuppression, we used filgrastim and its analogue, designed and produced by IEPOR, a recombinant granulocyte colony-stimulating factor (r-GCSF). Carbon granulated enterosorbent C2 was used for enteral sorption therapy (bulk density γ=0.18 g/cm3, diameter of granules 0.15-0.25 mm, BET pore surface – 2162 m2/g). All rats were sacrificed on the 17th day after carcinoma cells inoculation or on the 8th day after Melphalan injection. Results. Alkylating cytostatic agent caused severe leukopenia (by 95.7%), neutropenia (by 73.9%), and thrombocytopenia (by 84.9%) in the experimental rats. Mortality rate was 57%. Filgrastim and enterosorption with carbon oral adsorbent C2 increased the studied indices, but the most prominent results were observed when combination of both factors was used. Studied means did not affect the anti-tumor efficacy of Melphalan alone and in combination. Conclusions. Our results are perspective for further investigation of the efficacy of the combination of carbon oral adsorbents and hematopoietic cytokines in cases of ameliorate anti-cancer chemotherapy side effects, and its implementation into clinics.
粒细胞集落刺激因子和肠吸附在美法仑诱导的盖林癌移植大鼠骨髓抑制中的作用
背景。抗肿瘤药物的副作用(特别是白细胞减少和中性粒细胞减少)可能是有效治疗的主要限制因素。目标。本研究旨在研究粒细胞集落刺激因子(G-CSF)生物仿制药和颗粒碳口服吸附剂C2对melphalin诱导的移植Guerin癌大鼠骨髓抑制的骨髓保护能力。方法。5.5 mg/kg剂量的美法兰可促进移植Guerin癌大鼠骨髓抑制。为了对抗骨髓抑制,我们使用了由重组粒细胞集落刺激因子(r-GCSF) IEPOR设计和生产的非格昔汀及其类似物。采用碳粒型肠吸收剂C2进行肠内吸收治疗(体积密度γ=0.18 g/cm3,颗粒直径0.15 ~ 0.25 mm, BET孔表面积- 2162 m2/g)。所有大鼠于癌细胞接种后第17天或注射美法兰后第8天处死。结果。烷基化细胞抑制剂引起大鼠严重白细胞减少(95.7%)、中性粒细胞减少(73.9%)和血小板减少(84.9%)。死亡率为57%。非格司提姆和碳口腔吸附剂C2的肠道吸附均能提高研究指标,但两者联合使用效果最显著。研究方法不影响美法兰单用和联用的抗肿瘤效果。结论。我们的研究结果为进一步研究碳口服吸附剂与造血细胞因子联合使用在改善抗癌化疗副作用的情况下的疗效,并将其应用于临床提供了前景。
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