Cystic echinococcosis is a severe parasitic disease that commonly affects the liver and causes abscesses or rupture into the surrounding tissues, leading to multiple complications, such as shock, severe abdominal pain, and post-treatment abscess recurrence. Currently, there are no efficient measures to prevent these complications. We previously confirmed that arsenic trioxide (As₂O₃) exhibited in vitro cytotoxicity against Echinococcus granulosus protoscoleces. In the present study, we aimed to explore the mechanism of As₂O₃-induced E. granulosus protoscoleces apoptosis. After exposing E. granulosus protoscoleces to 0, 4, 6, and 8 μM As₂O₃, reactive oxygen species (ROS) level was detected by fluorescence microscopy; superoxide dismutase (SOD), and caspase-3 activities were measured; intracellular Ca²⁺ was detected by flow cytometry; GRP-78 and caspase-12 protein levels were measured by western blot analysis. Our results showed that the expression of caspase-3 was gradually increased and the expression of SOD was gradually decreased in As₂O₃-treated groups of protoscoleces. Simultaneously, fluorescence microscopy and flow cytometry showed that the ROS level and the intracellular Ca²⁺ level were increased in a time- and dose-dependent manner. Western blot analysis showed that the expressions of GRP-78 and caspase-12 were higher in As₂O₃-treated groups than in the control group. These results suggest that As₂O₃-induced apoptosis in E. granulosus protoscoleces is related to elevation of ROS level, disruption of intracellular Ca²⁺ homeostasis, and endoplasmic reticulum stress. These mechanisms can be targeted in the future by safer and more effective drugs to prevent recurrence of cystic echinococcosis.

Spillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate the in vitro efficacy of arsenic trioxide (ATO) against Echinococcus granulosus protoscolices. Protoscolices of E. granulosus were incubated in vitro with 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, the in vivo efficacy and possible side effects of ATO need to be explored.

Cystic echinococcosis (CE) is one of the most widespread and harmful zoonotic parasitic diseases, which most commonly affects the liver. In this study, we characterized multiple changes in mouse hepatocytes following treatment with excretory-secretory products (ESPs) of Echinococcus granulosus protoscoleces (Eg-PSCs) by a factorial experiment. The cell counting kit-8 assay (CCK-8), the 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry were used to detect the growth of hepatocytes. Inverted microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to observe the morphology and ultrastructure of hepatocytes. An automatic biochemical analyzer and an ELISA detection kit were used to determine six conventional hepatocyte enzymatic indices, the levels of five hepatocyte-synthesized substances, and the contents of glucose and lactate. Western blot analysis was conducted to analyze the protein expression of three apoptosis-related proteins, Bax, Bcl-2, cleaved caspase-3, and six glucose metabolism pathways rate-limiting enzymes in hepatocytes. The results showed that ESPs inhibited hepatocyte proliferation and promoted hepatocyte apoptosis. The cell membrane and microvilli of hepatocytes changed, and the nucleus, mitochondria and rough endoplasmic reticulum were damaged to varying degrees. The contents of iron, albumin (ALB), uric acid (UA) and urea were increased, and the activities of six enzymes in hepatocytes were increased except for the decrease of transferrin (TRF). The expression levels of all six key enzymes in the glucose metabolism pathway in hepatocytes were reduced. Our characterization provides a basis for further research on the pathogenesis, prevention and treatment of CE.

The purpose of this study was to establish the relationship between mitogen-activated protein kinase (MAPK) and Nrf2 signaling pathways in Echinococcus granulosus (E. granulosus). E. granulosus protoscoleces (PSCs) cultured in vitro were divided into different groups: a control group, PSCs were pretreated with various concentrations of propofol followed by exposure to hydrogen peroxide (H₂O₂), and PSCs were pretreated with MAPK inhibitors, then co-treated with propofol and incubated in the presence of H₂O₂. PSCs activity was observed under an inverted microscope and survival rate was calculated. Reactive oxygen species (ROS) was detected by fluorescence microscopy, western blotting was used to detect the expression of Nrf2, Bcl-2, and heme oxygenase 1 (HO-1) in the PSCs among different groups. Pretreatment of PSCs with 0–1 mM propofol for 8 h prevented PSCs death after exposure to 0.5 mM H₂O₂. PSCs were pretreated with PD98059, SB202190, or SP600125 for 2 h, co-treated with propofol for an additional 8 h, and then exposed to 0.5 mM H₂O₂ for 6 h. On day 6, the PSCs viability was 42% and 39% in the p38 and JNK inhibitor groups, respectively. Additionally, pretreatment with propofol significantly attenuated the generation of ROS following H₂O₂ treatment. Propofol increased the expression of Nrf2, HO-1, and BCL2 compared with that of the control group. Pretreatment PSCs with SP600125 or SB202190, co-incubation with propofol and H₂O₂, can reduce the expression of Nrf2, HO-1, and BCL2 (p < 0.05). These results suggest that propofol induces an upregulated expression of HO-1 and Nrf2 by activation of the JNK and p38 MAPK signaling pathways. This study highlights the cross role of metabolic regulation of ROS signaling and targeting signalling pathways that may provide a promising strategy for the treatment of E. granulosus disease.