Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis

Rafaella R. Costa, João A. Oliveira-da-Silva, Thiago A.R. Reis, Grasiele S.V. Tavares, Débora V.C. Mendonça, Camila S. Freitas, Daniela P. Lage, Vívian T. Martins, Luciana M.R. Antinarelli, Amanda S. Machado, Raquel S. Bandeira, Fernanda Ludolf, Thaís T.O. Santos, Rory C.F. Brito, Maria V. Humbert, Daniel Menezes-Souza, Mariana C. Duarte, Miguel A. Chávez-Fumagalli, Bruno M. Roatt, Elaine S. CoimbraEduardo A.F. Coelho

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)133-147
Number of pages15
JournalMedical Microbiology and Immunology
Volume210
Issue number2-3
DOIs
StatePublished - Jun 2021

Keywords

  • Acarbose
  • Drug repositioning
  • Leishmania infantum
  • Miltefosine
  • Treatment
  • Visceral leishmaniasis

Fingerprint

Dive into the research topics of 'Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis'. Together they form a unique fingerprint.

Cite this