Dataset Information

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

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.

SUBMITTER: Mahanty S

PROVIDER: S-EPMC3019660 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mahanty S S Paredes A A Marzal M M Gonzalez E E Rodriguez S S Dorny P P Guerra-Giraldez C C Garcia H H HH Nash T T

Antimicrobial agents and chemotherapy 20101101 1

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), t ...[more]

PMID: 21041508

Similar Datasets

Project description:Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T. solium and T. saginata may help to elucidate why cysticercosis can occur from one and not the other. The aim of this study was to use in vitro culture assays and in vivo models to study the differences in the development of the T. solium and T. saginata oncosphere. Furthermore, this study aimed to evaluate the expression of cytokines and metalloproteinases (MMPs) in human peripheral blood mononuclear cells (PBMCs), which were stimulated by these oncospheres and PO antigens. T. solium and T. saginata activated oncospheres (AO) were cultured in INT-407 and HCT-8 intestinal cells for 180 days. The T. solium began to die while the T. saginata grew for 180 days and developed to cysticerci in INT-407 cells. Rats were inoculated intracranially with AO and PO forms of either T. saginata or T. solium. Rats infected with T. solium AO and PO forms developed neurocysticercosis (NCC), while those infected with the T. saginata did not. Human PMBCs were stimulated with antigens of AO and PO forms of both species, and the production of cytokines and metalloproteinases (MMPs) was measured. The T. solium AO antigen stimulated a higher production of IL-4, IL-5, IL-13, IFN-γ, and IL-2 cytokines compared to T. saginata AO. In the PO form, the T. saginata PO antigen increased the production of IL-4, IL-5, IL-13, IFN-γ, IL-1β, IL-6, IL-10, TNF-α and IL-12 cytokines compared to T. solium, suggesting that this global immune response stimulated by different forms could permit survival or destruction of the parasite depending of their life-cycle stage. Regarding MMPs, T. solium AO antigen stimulated a higher production of MMP-9 compared to T. saginata AO antigen, which may be responsible for altering the permeability of intestinal cells and facilitating breakdown of the blood-brain barrier during the process of invasion of host tissue.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets