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高活性碳肠吸附剂可介导对小鼠Lewis肺癌相关副肿瘤综合征的抑制作用。

Highly activated carbon enterosorbent mediates the suppression of paraneoplastic syndrome associated with Lewis lung carcinoma in mice.

作者信息

Sarnatskaya V V, Sakhno L, Paziuk L M, Yushko L A, Rodionova N K, Maslenniy V N, Sidorenko A S, Nikolaev V

机构信息

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.

Department of Cytology, Histology and Developmental Biology, Institute of Biology, Taras Shevchenko National University of Kyiv, Kyiv 03608, Ukraine.

出版信息

Exp Oncol. 2018 Mar;40(1):33-41.

Abstract

AIM

To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC).

MATERIALS AND METHODS

The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7 day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry.

RESULTS

Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine.

CONCLUSION

The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes.

摘要

目的

研究肠吸附对Lewis肺癌(LLC)小鼠副肿瘤综合征发展的影响。

材料与方法

对移植了LLC的雄性C57/BL6小鼠进行研究。从肿瘤细胞移植后第7天开始,每天口服给予HSGD的高活性粉末级分作为肠吸附剂,剂量为0.625 g/kg,持续两周。在完成肠吸附疗程后,采用标准方法进行血常规和骨髓象分析、重要器官的形态学改变、过氧化氢酶和超氧化物歧化酶活性、血液生化分析以及氢过氧化物、丙二醛、晚期氧化蛋白产物的定量分析。通过差示扫描量热法评估血浆蛋白的配体负载。

结果

给予肠吸附剂可抑制LLC生长,并使肺转移瘤数量减少近2倍(p < 0.05)。给予肠吸附剂后,骨髓中粒细胞系活化,有丝分裂活性增强近3倍。红细胞系指标和骨髓细胞密度保持不变。肠吸附疗程后,外周血的研究生化指标表明内源性中毒和氧化应激水平降低,肾脏功能状态改善,红细胞膜抵抗力增加,血浆转运蛋白的配体负载降低。肾脏和肝脏的形态结构证实了肠吸附的显著积极作用。给予肠吸附剂两周后,胃底、小肠和大肠切片的形态学检查数据显示其安全性高且能从肠道正常排空。

结论

在LLC小鼠中进行为期两周的肠吸附疗程可抑制肿瘤生长和转移,使骨髓造血正常化。肠吸附对肾脏和肝脏的结构形态指标和再生潜力产生积极影响,减轻氧化应激表现,降低内源性中毒水平,促进白蛋白分子去配体和红细胞膜减负。

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