In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus
Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v58_n9_p5146_Nicolao http://hdl.handle.net/20.500.12110/paper_00664804_v58_n9_p5146_Nicolao |
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paper:paper_00664804_v58_n9_p5146_Nicolao2023-06-08T15:06:11Z In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus calcium multidrug resistance protein placebo steroid receptor tamoxifen citrate calcium multidrug resistance protein steroid receptor tamoxifen animal experiment animal model anthelmintic activity article body weight calcium homeostasis chemoprophylaxis concentration (parameters) controlled study drug efficacy echinococcosis Echinococcus granulosus female in vitro study in vivo study infection prevention larval stage metacestode mouse nonhuman nucleotide sequence parasite survival priority journal weight reduction animal antagonists and inhibitors drug effects echinococcosis homeostasis larva metabolism Animals Calcium Echinococcosis Echinococcus granulosus Female Homeostasis Larva Mice P-Glycoprotein Receptors, Steroid Tamoxifen Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment. Copyright © 2014, American Society for Microbiology. All Rights Reserved. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v58_n9_p5146_Nicolao http://hdl.handle.net/20.500.12110/paper_00664804_v58_n9_p5146_Nicolao |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
calcium multidrug resistance protein placebo steroid receptor tamoxifen citrate calcium multidrug resistance protein steroid receptor tamoxifen animal experiment animal model anthelmintic activity article body weight calcium homeostasis chemoprophylaxis concentration (parameters) controlled study drug efficacy echinococcosis Echinococcus granulosus female in vitro study in vivo study infection prevention larval stage metacestode mouse nonhuman nucleotide sequence parasite survival priority journal weight reduction animal antagonists and inhibitors drug effects echinococcosis homeostasis larva metabolism Animals Calcium Echinococcosis Echinococcus granulosus Female Homeostasis Larva Mice P-Glycoprotein Receptors, Steroid Tamoxifen |
| spellingShingle |
calcium multidrug resistance protein placebo steroid receptor tamoxifen citrate calcium multidrug resistance protein steroid receptor tamoxifen animal experiment animal model anthelmintic activity article body weight calcium homeostasis chemoprophylaxis concentration (parameters) controlled study drug efficacy echinococcosis Echinococcus granulosus female in vitro study in vivo study infection prevention larval stage metacestode mouse nonhuman nucleotide sequence parasite survival priority journal weight reduction animal antagonists and inhibitors drug effects echinococcosis homeostasis larva metabolism Animals Calcium Echinococcosis Echinococcus granulosus Female Homeostasis Larva Mice P-Glycoprotein Receptors, Steroid Tamoxifen In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| topic_facet |
calcium multidrug resistance protein placebo steroid receptor tamoxifen citrate calcium multidrug resistance protein steroid receptor tamoxifen animal experiment animal model anthelmintic activity article body weight calcium homeostasis chemoprophylaxis concentration (parameters) controlled study drug efficacy echinococcosis Echinococcus granulosus female in vitro study in vivo study infection prevention larval stage metacestode mouse nonhuman nucleotide sequence parasite survival priority journal weight reduction animal antagonists and inhibitors drug effects echinococcosis homeostasis larva metabolism Animals Calcium Echinococcosis Echinococcus granulosus Female Homeostasis Larva Mice P-Glycoprotein Receptors, Steroid Tamoxifen |
| description |
Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment. Copyright © 2014, American Society for Microbiology. All Rights Reserved. |
| title |
In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| title_short |
In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| title_full |
In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| title_fullStr |
In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| title_full_unstemmed |
In Vitro and in Vivo effects of tamoxifen against larval stage Echinococcus granulosus |
| title_sort |
in vitro and in vivo effects of tamoxifen against larval stage echinococcus granulosus |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v58_n9_p5146_Nicolao http://hdl.handle.net/20.500.12110/paper_00664804_v58_n9_p5146_Nicolao |
| _version_ |
1768542028088475648 |