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评价贯叶连翘叶提取物及其凝集素(SteLL)在肉瘤 180 荷瘤小鼠中的抗肿瘤活性和毒性。

Evaluation of antitumor activity and toxicity of Schinus terebinthifolia leaf extract and lectin (SteLL) in sarcoma 180-bearing mice.

机构信息

Campus Amilcar Ferreira Sobral, Universidade Federal do Piauí, Floriano, Piauí, Brazil; Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.

Laboratório de Oncologia Experimental, Universidade Federal do Vale do São Francisco, Petrolina, Pernambuco, Brazil.

出版信息

J Ethnopharmacol. 2019 Apr 6;233:148-157. doi: 10.1016/j.jep.2019.01.011. Epub 2019 Jan 15.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Schinus terebinthifolia Raddi is a plant broadly used in folk medicine and the use of its leaf extract as an antitumor agent has been reported.

AIM OF THE STUDY

To evaluate the antitumor potential and the toxicity of saline extract (SE) and lectin (SteLL) from S. terebinthifolia leaves in sarcoma 180-bearing mice.

MATERIALS AND METHODS

Cytotoxicity to sarcoma 180 cells was tested in vitro, and antitumor assay was performed using Swiss female mice. The treatments (0.15 M NaCl, negative control; methotrexate 1.5 mg/kg, positive control; SE 100 mg/kg; SteLL 1 and 5 mg/kg) by intraperitoneal injections started on the 8th day after tumor inoculation and lasted 7 days. It was analyzed: tumor weight; number and gauge of tumor vessels; hematological and biochemical parameters; histopathological changes; and occurrence of micronuclei in bone marrow cells.

RESULTS

SE and SteLL showed IC values (concentrations that reduced cell viability to 50%) of 301.65 and 8.30 μg/mL, respectively. The lectin was able to induce apoptosis. Treatments with the extract and lectin caused a 57.6-73.6% reduction in tumor weight, which was not significantly different from the reduction in the methotrexate group. Tumors of animals treated with SteLL at 5 mg/kg showed reduced number of secondary vessels while the gauge was lower in all treated groups. In the groups treated with SteLL, tumors showed reduced and slightly vascularized parenchyma, with necrosis in the center and at the periphery. No alterations in the blood levels of urea, creatine, and glucose were detected while serum AST level was moderately increased in the SE group. Histopathological analysis revealed vacuolization and steatosis in the liver of animals treated with the extract and lectin. In addition, the treatments with SE and SteLL resulted in the reduction of filtration space and alterations in tubular architecture in kidneys. In respect to hematological parameters, it was only detected increase in the number of monocytes in SE group. The extract and lectin did not induce the formation of micronuclei in the bone marrow cells.

CONCLUSIONS

SE and SteLL had antitumor effect against sarcoma 180 without inducing hematological changes and genotoxic effects in mice; however, some degree of hepatic and renal toxicity was observed, suggesting the evaluation of drug delivery strategies in the future.

摘要

民族药理学相关性

Schinus terebinthifolia Raddi 是一种广泛用于民间医学的植物,其叶提取物作为抗肿瘤剂的用途已有报道。

研究目的

评估盐水提取物 (SE) 和凝集素 (SteLL) 对肉瘤 180 荷瘤小鼠的抗肿瘤潜力和毒性。

材料和方法

在体外测试对肉瘤 180 细胞的细胞毒性,并使用瑞士雌性小鼠进行抗肿瘤测定。从肿瘤接种后第 8 天开始,通过腹腔注射进行治疗(0.15M NaCl,阴性对照;甲氨蝶呤 1.5mg/kg,阳性对照;SE 100mg/kg;SteLL 1 和 5mg/kg),持续 7 天。分析:肿瘤重量;肿瘤血管的数量和直径;血液学和生化参数;组织病理学变化;骨髓细胞微核的发生。

结果

SE 和 SteLL 的 IC 值(将细胞活力降低至 50%的浓度)分别为 301.65 和 8.30μg/mL。凝集素能够诱导细胞凋亡。提取物和凝集素处理导致肿瘤重量减少 57.6-73.6%,与甲氨蝶呤组的减少无显著差异。用 5mg/kg SteLL 处理的肿瘤次级血管数量减少,而所有治疗组的直径均较低。用 SteLL 处理的肿瘤显示出减少的、轻度血管化的实质,中心和外围有坏死。在 SE 组中,血清 AST 水平中度升高,但未检测到尿素、肌酸和葡萄糖血液水平的改变。组织病理学分析显示,用提取物和凝集素处理的动物的肝脏出现空泡化和脂肪变性。此外,SE 和 SteLL 的处理导致肾脏滤过空间减少和管状结构改变。就血液学参数而言,仅在 SE 组中检测到单核细胞数量增加。提取物和凝集素未在骨髓细胞中诱导微核形成。

结论

SE 和 SteLL 对肉瘤 180 具有抗肿瘤作用,而不会在小鼠中引起血液学变化和遗传毒性作用;然而,观察到一定程度的肝和肾毒性,表明未来需要评估药物输送策略。

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