Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis
| Autor: | Rafaella R Costa, Elaine Soares Coimbra, Grasiele S.V. Tavares, João A. Oliveira-da-Silva, Bruno Mendes Roatt, Daniel Menezes-Souza, Fernanda Ludolf, Rory Cristiane Fortes de Brito, Maria Victoria Humbert, Vívian T. Martins, Miguel A. Chávez-Fumagalli, Luciana M.R. Antinarelli, Eduardo A.F. Coelho, Camila S. Freitas, Amanda S. Machado, Thaís T.O. Santos, Raquel S. Bandeira, Mariana C. Duarte, Daniela P. Lage, Thiago A.R. Reis, Débora V.C. Mendonça |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Phosphorylcholine 030106 microbiology Immunology Antiprotozoal Agents Pharmacology Parasite Load Mice 03 medical and health sciences In vivo Animals Immunology and Allergy Medicine Leishmania infantum Amastigote Micelles Original Investigation Acarbose Visceral leishmaniasis Mice Inbred BALB C Miltefosine biology business.industry Drug repositioning Immunity General Medicine biology.organism_classification medicine.disease In vitro eye diseases Treatment stomatognathic diseases Treatment Outcome 030104 developmental biology Toxicity Leishmaniasis Visceral Female Reactive Oxygen Species business medicine.drug |
| Zdroj: | Medical Microbiology and Immunology |
| Popis: | Treatment against visceral leishmaniasis (VL) is mainly hampered by drug toxicity, long treatment regimens and/or high costs. Thus, the identification of novel and low-cost antileishmanial agents is urgent. Acarbose (ACA) is a specific inhibitor of glucosidase-like proteins, which has been used for treating diabetes. In the present study, we show that this molecule also presents in vitro and in vivo specific antileishmanial activity against Leishmania infantum. Results showed an in vitro direct action against L. infantum promastigotes and amastigotes, and low toxicity to mammalian cells. In addition, in vivo experiments performed using free ACA or incorporated in a Pluronic ® F127-based polymeric micelle system called ACA/Mic proved effective for the treatment of L. infantum-infected BALB/c mice. Treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes when compared to the controls, as well as the development of antileishmanial Th1-type humoral and cellular responses based on high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and IgG2a isotype antibodies. In addition, ACA or ACA-treated animals suffered from low organ toxicity. Treatment with ACA/Mic outperformed treatments using either Miltefosine or free ACA based on parasitological and immunological evaluations performed one and 15 days post-therapy. In conclusion, data suggest that the ACA/Mic is a potential therapeutic agent against L. infantum and merits further consideration for VL treatment. |
| Databáze: | OpenAIRE |
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