Shevchuk O O, Posokhova K A, Sidorenko A S, Bardakhivskaya K I, Maslenny V M, Yushko L A, Chekhun V F, Nikolaev V G
I.Ya. Horbachevsky Ternopil State Medical University, Ternopil 46001, Ukraine.
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2014 Jun;36(2):94-100.
One of the most prominent side effects of intensive cancer chemotherapy is bone marrow suppression which is an independent negative prognostic factor for the time to tumor progression. The aim of the study was to evaluate the myeloprotective possibilities of carbon enterosorbents in the case of usage of alkilating drug melphalan (L-PAM).
L-PAM was injected intravenously to healthy inbred rats to cause the myelosuppression. 3 days before and 7 days after this, suspension of two types of carbon granulated enterosorbents were administered per os one time per day. On 8(th) day after L-PAM injection, the rats were weighted and blood and liver tissue were taken under Ketamine general anesthesia for biochemical examination. Peripheral blood smears were made also.
Melphalan at a dose of 3 mg/kg causes expressed myelotoxic reaction: leucopenia, decreasing of erythrocytes, hemoglobin and platelets counts. Even on 8(th) day after single injection of this cytostatic we can detect expressed signs of oxidative stress like increasing of hydroperoxides, TBA-reactive substances, and decreasing of activity and level of main endogenic antioxidants - superoxide dismutase (SOD), catalase and reduced glutathione. L-PAM causes also the violation of kidney function such as increase of urea and creatinine level; and rising of endogenic intoxication with elevation of middle mass molecules level. In a dose of 3 mg/kg melphalan has no negative influence on liver function on 8(th) day of experiment. Enterosorption with carbon enterosorbents C1 (bulk density γ = 0.28 g/cm(3), granules diameter 0.15-0.25 mm, BET pore surface 1719 m(2)/g, therapeutic dosage 1400 mg/kg) and C2 (bulk density γ = 0.18 g/cm(3), granules diameter 0.15-0.25 mm, BET pore surface 2162 m(2)/g, therapeutic dosage 900 mg/kg) diminishes and mitigates negative side effects caused by single intravenous injection of melphalan. Carbon enterosorbent C2 have rather more expressed positive effect than C1 for practically all indices. The most important curative effect due to C2 administration is prominent myeloprotection of bone marrow of experimental animals.
Carbon enterosorbent C2 is promising and perspective sorbent for prophylaxis and treatment of side effects of cytostatic chemotherapy including myelotoxicity, mucositis, kidney injuries, gonadotoxicity, etc.
强化癌症化疗最显著的副作用之一是骨髓抑制，它是肿瘤进展时间的一个独立负面预后因素。本研究的目的是评估在使用烷化剂美法仑（L-PAM）的情况下碳质肠吸附剂的骨髓保护作用。
向健康的近交系大鼠静脉注射L-PAM以引起骨髓抑制。在此之前3天和之后7天，每天经口给予两种类型的碳质颗粒肠吸附剂悬浮液。在注射L-PAM后的第8天，对大鼠称重，并在氯胺酮全身麻醉下采集血液和肝脏组织进行生化检查。同时制作外周血涂片。
剂量为3mg/kg的美法仑会引起明显的骨髓毒性反应：白细胞减少、红细胞、血红蛋白和血小板计数降低。即使在单次注射这种细胞抑制剂后的第8天，我们也能检测到氧化应激的明显迹象，如氢过氧化物、TBA反应性物质增加，以及主要内源性抗氧化剂——超氧化物歧化酶（SOD）、过氧化氢酶和还原型谷胱甘肽的活性和水平降低。L-PAM还会导致肾功能损害，如尿素和肌酐水平升高；以及随着中分子水平升高内源性中毒加剧。在实验的第8天，剂量为3mg/kg的美法仑对肝功能没有负面影响。用碳质肠吸附剂C1（堆积密度γ = 0.28g/cm³，颗粒直径0.15 - 0.25mm，BET孔表面积1719m²/g，治疗剂量1400mg/kg）和C2（堆积密度γ = 0.18g/cm³，颗粒直径0.15 - 0.25mm，BET孔表面积2162m²/g，治疗剂量900mg/kg）进行肠吸附可减少并减轻单次静脉注射美法仑引起的负面副作用。对于几乎所有指标，碳质肠吸附剂C2的积极作用比C1更明显。由于给予C2而产生的最重要治疗效果是对实验动物骨髓有显著的骨髓保护作用。
碳质肠吸附剂C2是一种有前景且有潜力的吸附剂，可用于预防和治疗细胞抑制剂化疗的副作用，包括骨髓毒性、粘膜炎、肾损伤、性腺毒性等。
