Advanced search
1 file | 755.12 KB

Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts

Author
Organization
Abstract
Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium cysts in vitro. Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic) drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination, whereas ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts, and both drugs inhibited AP secretion at concentrations of 5 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by T. solium cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit.
Keywords
NEUROCYSTICERCOSIS, INVITRO, GRANULOSUS, CRASSICEPS CYSTS, ECHINOCOCCUS-MULTILOCULARIS METACESTODES, VIVO, COMBINATION THERAPY, CYSTICERCOSIS, SULFOXIDE, PROTOSCOLECES

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 755.12 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Mahanty, S, A Paredes, M Marzal, E Gonzalez, S Rodriguez, Pierre Dorny, C Guerra-Giraldez, HH Garcia, and T Nash. 2011. “Sensitive in Vitro System to Assess Morphological and Biochemical Effects of Praziquantel and Albendazole on Taenia Solium Cysts.” Antimicrobial Agents and Chemotherapy 55 (1): 211–217.
APA
Mahanty, S, Paredes, A., Marzal, M., Gonzalez, E., Rodriguez, S., Dorny, P., Guerra-Giraldez, C., et al. (2011). Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55(1), 211–217.
Vancouver
1.
Mahanty S, Paredes A, Marzal M, Gonzalez E, Rodriguez S, Dorny P, et al. Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2011;55(1):211–7.
MLA
Mahanty, S, A Paredes, M Marzal, et al. “Sensitive in Vitro System to Assess Morphological and Biochemical Effects of Praziquantel and Albendazole on Taenia Solium Cysts.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 55.1 (2011): 211–217. Print.
@article{1154230,
  abstract     = {Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium cysts in vitro. Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic) drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination, whereas ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts, and both drugs inhibited AP secretion at concentrations of 5 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by T. solium cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit.},
  author       = {Mahanty, S and Paredes, A and Marzal, M and Gonzalez, E and Rodriguez, S and Dorny, Pierre and Guerra-Giraldez, C and Garcia, HH and Nash, T},
  issn         = {0066-4804},
  journal      = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
  keyword      = {NEUROCYSTICERCOSIS,INVITRO,GRANULOSUS,CRASSICEPS CYSTS,ECHINOCOCCUS-MULTILOCULARIS METACESTODES,VIVO,COMBINATION THERAPY,CYSTICERCOSIS,SULFOXIDE,PROTOSCOLECES},
  language     = {eng},
  number       = {1},
  pages        = {211--217},
  title        = {Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts},
  url          = {http://dx.doi.org/10.1128/AAC.00761-10},
  volume       = {55},
  year         = {2011},
}

Altmetric
View in Altmetric
Web of Science
Times cited: