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成功管理伊立替康减毒动物:一种基于蛋白质的辅助植物药。

Successful Pre-Clinical Management of Irinotecan-Debilitated Animals: A Protein- Based Accessory Phytomedicine.

机构信息

Departamento de Fisiologia e Farmacologia, Federal University of Ceara, Campus do Porangabuçú. Fortaleza, Ceará, Brazil.

Departamento de Bioquímica e Biologia Molecular, Federal University of Ceara, Campus do Pici. Fortaleza, Ceará, Brazil.

出版信息

Anticancer Agents Med Chem. 2022;22(18):3163-3171. doi: 10.2174/1871520622666220610115617.

DOI:10.2174/1871520622666220610115617
PMID:35692152
Abstract

BACKGROUND

Calotropis procera is a laticiferous plant (Apocynaceae) found in tropical regions all over the world. The ultrastructural characteristics of laticifers, their restricted distribution among different taxonomic groups, and in some species in each clade, as peptidases from latex, make them very attractive for biological analysis.

OBJECTIVE

The study aims to investigate the effects of LP-PII-IAA (laticifer protein (LP) sub-fraction II (PII) of C. procera presenting an iodoacetamide-inhibited cysteine proteinase activity) on irinotecan-induced intestinal mucositis, a serious adverse effect of this medicine for the treatment of cancer.

METHODS

LP-PII-IAA is composed of closely related isoforms (90%) of peptidases derived from catalysis and an osmotin protein (5%). Animals receiving co-administration of LP-PII-IAA presented a significant decrease in mortality, absence of diarrhea, histological preservation, and normalization of intestinal functions.

RESULTS

Clinical homeostasis was accompanied by a reduction in MPO activity and declined levels of IL-1β, IL-6 and KC, while the IL-10 level increased in LP-PII-IAA-treated animals. COX-2 and NF-kB immunostaining was reduced and the levels of oxidative markers (GSH, MDA) were normalized in animals that received LP-PII-IAA.

CONCLUSION

We suggest that peptidases from the latex of Calotropis procera were instrumental in the suppression of the adverse clinical and physiological effects of irinotecan.

摘要

背景

牛奶菜是一种乳汁管植物(夹竹桃科),分布于世界各地的热带地区。乳汁管的超微结构特征、在不同分类群中的有限分布,以及在每个分支中的某些物种中作为乳蛋白酶,使它们非常适合进行生物分析。

目的

本研究旨在探讨 LP-PII-IAA(牛奶菜乳汁管蛋白(LP)亚部分 II(PII),具有碘乙酰胺抑制的半胱氨酸蛋白酶活性)对伊立替康诱导的肠道黏膜炎的影响,伊立替康是治疗癌症的一种严重不良反应。

方法

LP-PII-IAA 由密切相关的同工型(90%)的蛋白酶和 osmotin 蛋白(5%)组成。接受 LP-PII-IAA 共同给药的动物死亡率显著降低,没有腹泻,组织学保存,以及肠道功能正常化。

结果

临床内稳态伴随着 MPO 活性降低,IL-1β、IL-6 和 KC 水平下降,而 LP-PII-IAA 治疗动物的 IL-10 水平增加。COX-2 和 NF-kB 免疫染色减少,接受 LP-PII-IAA 治疗的动物的氧化标志物(GSH、MDA)水平正常化。

结论

我们认为牛奶菜乳汁中的蛋白酶在抑制伊立替康的不良临床和生理作用方面发挥了重要作用。

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