Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo
Copyright © 2020 Elsevier B.V. All rights reserved..
In view of a growing need for new treatment options for human cystic echinococcosis (CE), we aimed to investigate the efficacy of mTOR pathway inhibitors against CE in vitro and in vivo. Among the seven mTOR inhibitors evaluated, tacrolimus (TAC) showed significant dose- and time-dependent killing of cultured protoscoleces and cysts in vitro. Notably, the oral administration of TAC (4 mg/kg/day) to CE mice model highly effectively reduced both the weight and number of parasitic cysts. Transmission electron microscopy revealed that TAC destroys the ultrastructure of cysts, both in vitro and in vivo. Furthermore, TAC had no significant effect on blood glucose, body weight, liver, or kidney functions in mice. We further observed that the ATP levels and glucose content of cysts reduced upon TAC treatment, indicating that inhibiting mTORC1 activity possibly affects glucose metabolism in the cysts of mice. Based on our experimental data, TAC emerged as a promising anti-cyst drug that efficiently inhibits the growth of cysts.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:212 |
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Enthalten in: |
Acta tropica - 212(2020) vom: 30. Dez., Seite 105708 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Muhedier, Muzhabaier [VerfasserIn] |
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Links: |
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Themen: |
Anti-cystic echinococcosis |
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Anmerkungen: |
Date Completed 05.03.2021 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.actatropica.2020.105708 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM315279028 |
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520 | |a In view of a growing need for new treatment options for human cystic echinococcosis (CE), we aimed to investigate the efficacy of mTOR pathway inhibitors against CE in vitro and in vivo. Among the seven mTOR inhibitors evaluated, tacrolimus (TAC) showed significant dose- and time-dependent killing of cultured protoscoleces and cysts in vitro. Notably, the oral administration of TAC (4 mg/kg/day) to CE mice model highly effectively reduced both the weight and number of parasitic cysts. Transmission electron microscopy revealed that TAC destroys the ultrastructure of cysts, both in vitro and in vivo. Furthermore, TAC had no significant effect on blood glucose, body weight, liver, or kidney functions in mice. We further observed that the ATP levels and glucose content of cysts reduced upon TAC treatment, indicating that inhibiting mTORC1 activity possibly affects glucose metabolism in the cysts of mice. Based on our experimental data, TAC emerged as a promising anti-cyst drug that efficiently inhibits the growth of cysts | ||
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