In vitro and in vivo Effects of Artesunate on Echinococcus granulosus Protoscoleces and Metacestodes
| Autor: | Limei Wen, Yafen Li, Chunyan Tian, Jianhua Wang, Jun Zhao, Guo-dong Lv, Gong Yuehong, Haiya Zheng, Gao Huijing, Bei Chen, Shuai Lu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmaceutical Science medicine.disease_cause Albendazole Superoxide dismutase Andrology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Oral administration In vivo Drug Discovery medicine Echinococcus granulosus Pharmacology chemistry.chemical_classification Reactive oxygen species biology Glutathione biology.organism_classification 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Oxidative stress medicine.drug |
| Zdroj: | Drug Design, Development and Therapy. 14:4685-4694 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s254166 |
| Popis: | Background In this study, we aim to investigate the efficiency of artesunate (AS) on Echinococcus granulosus protoscoleces and metacestodes. Methods For the in vitro assay, the eosin dye exclusion test and transmission electron microscope (TEM) were utilized to evaluate the effects of AS against protoscoleces (PSCs) from Echinococcus granulosus. In addition, mortality, ultrastructure change, reactive oxygen species (ROS) content and DNA damage were measured in order to explore the anti-echinococcosis mechanism of AS. For the in vivo assay, CE-infected mice were divided into model group, albendazole (ABZ) group (200 mg/kg), low AS (AS-L) group (50 mg/kg), moderate AS (AS-M) group (100 mg/kg), and high AS (AS-H) group (200 mg/kg). Upon 6 weeks oral administration, wet weight of cysts and the ultrastructural changes of cystic wall were utilized to evaluate the effects of AS on metacestodes. In addition, the liver biochemical parameters, tumor necrosis factor-α (TNF-α), glutathione/glutathione oxidized (GSH/GSSG) ratio in serum, and H2O2, total superoxide dismutase (T-SOD) in cyst fluid were detected. Results Both in vivo and in vitro experiments showed that AS showed anti-parasitic effects on CE. The AS could elevate the ROS level in the PSCs, which then resulted in obvious DNA damages. AS could significantly improve the liver biochemical parameters in infected mice compared with the model group (P < 0.05). Compared with the model group, AS-M and AS-H decrease the TNF-α content (P < 0.05); AS-H group significantly decrease in the serum GSH/GSSG ratio (P < 0.05). The content of H2O2 in hydatid fluid treated by AS showed significant decrease compared with the model group (P < 0.01), while the T-SOD level showed significant elevation compared with model group (P < 0.01). Conclusion In this study, we confirmed that the effects of AS on Echinococcus granulosus protoscoleces and metacestodes may be related to the DNA damages induced by oxidative stress, which provided solid information for the research and development of drugs for cystic echinococcosis. |
| Databáze: | OpenAIRE |
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