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Abstract
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.
Abbreviations
ABZ, albendazole; ART, Artemisinin; AS, artesunate; ALT, alanine aminotransferase; AST, and aspartate aminotransferase; CE, cystic echinococcosis; DBIL, direct bilirubin; GSH/GSSG, glutathione/glutathione oxidized; H2O2, hydrogen peroxide; LMA, low-melting point agarose; NMA, normal-melting point agarose; PI, propidium iodide; PSCs, protoscoleces; ROS, reactive oxygen species; RPS9, ribosomal protein S9; TBIL, total bilirubin; TEM, transmission electron microscope; TNF-α, tumor necrosis factor-α; T-SOD, total superoxide dismutase.
Data Sharing Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Ethics Approval and Consent to Participate
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Consent for Publication
Informed consent was obtained from all individual participants included in the study.
Disclosure
The authors declare that they have no competing interests.