TY - JOUR
T1 - In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto
AU - Bakhtiar, Nayer Mehdizad
AU - Akbarzadeh, Abolfazl
AU - Ahmadpour, Ehsan
AU - Mahami-Oskouei, Mahmoud
AU - Casulli, Adriano
AU - Norouzi, Roghayeh
AU - Asadi, Milad
AU - Ebrahimi, Mina
AU - Asadi, Nahideh
AU - Rodrigues Oliveira, Sonia M.
AU - de Lourdes Pereira, Maria
AU - Spotin, Adel
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/12
Y1 - 2022/12
N2 - Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. Methods: We evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD groups. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 μg/mL ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 μg/mL ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. Conclusions: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 μg/mL ABZ-β-CD compared to ABZ alone. This provides new insights into the use of nanostructured β-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.
AB - Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. Methods: We evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD groups. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 μg/mL ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 μg/mL ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. Conclusions: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 μg/mL ABZ-β-CD compared to ABZ alone. This provides new insights into the use of nanostructured β-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.
KW - Albendazole
KW - Apoptosis
KW - Arginase
KW - Echinococcus granulosus
KW - Protoscoleces
KW - Thioredoxin peroxidase
KW - β-Cyclodextrin
UR - http://www.scopus.com/inward/record.url?scp=85142197663&partnerID=8YFLogxK
U2 - 10.1016/j.exppara.2022.108428
DO - 10.1016/j.exppara.2022.108428
M3 - Article
C2 - 36384195
SN - 0014-4894
VL - 243
JO - Experimental Parasitology
JF - Experimental Parasitology
M1 - 108428
ER -