Abstract
The purpose of the present study was to evaluate the efficacy of the treatment with a recombinant cysteine proteinase from Leishmania, rldccys1, associated with allopurinol or miltefosine on Leishmania (Leishmania) infantum chagasi–infected hamsters. Golden Syrian hamsters infected with L. (L.) infantum chagasi were treated with either miltefosine (46 mg/kg) or allopurinol (460 mg/kg) alone by oral route or associated with rldccys1 (150 µg/hamster) by subcutaneous route for 30 days. Infected hamsters were also treated with miltefosine (46 mg/kg) plus rldccys1 (150 µg/hamster) for 30 days (phase 1) followed by two additional doses of rldccys1 (250 µg/hamster) (phase 2). After the end of treatment, the animals were analyzed for parasite load, body weight, serum levels of immunoglobulins, cytokine expression, and drug toxicity. The data showed a significant decrease of parasite load in infected hamsters treated with allopurinol or miltefosine alone or associated with rldccys1, as well as in those treated with rldccys1 alone. Significantly lower levels of serum IgG were detected in hamsters treated with allopurinol plus rldccys1. The treatment with miltefosine associated with rldccys1 prevented relapse observed in animals treated with miltefosine alone. A significant loss of body weight was detected only in some hamsters treated with miltefosine for 1 month and deprived of this treatment for 15 days. There were no significant differences in transcript expression of IFN-γ and IL-10 in any of treated groups. Neither hepatotoxicity nor nephrotoxicity was observed among controls and treated groups. These findings open perspectives to further explore this immunochemotherapeutic schedule as an alternative for treatment of visceral leishmaniasis.
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We are grateful to Luiz Severino da Silva and Sandra Regina dos Reis for the technical assistance.
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This work was supported by grant #2018/10.373–2, São Paulo Research Foundation (FAPESP). Fabiana Rodrigues de Santana (2017/06350–4) was supported by FAPESP fellowship. Danielle Aparecida Marino da Silva (88882.330528/2019–01) was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) fellowship.
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Fabiana Rodrigues de Santana designed and performed the experiments, analyzed and interpreted the data, and wrote and reviewed the manuscript. Danielle Aparecida Marino da Silva assisted in carrying out the experiments. Simone Katz technically supported all stages of the project. Cristina Mary Orikaza technically supported the RT-qPCR methodology. Katia Cristina Oliveira contributed to the interpretation of the data and revision of the manuscript, and Clara Lúcia Barbiéri conceived the work, contributed to the interpretation of the data, and wrote and reviewed the manuscript.
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de Santana, F.R., da Silva, D.A.M., Katz, S. et al. A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model. Parasitol Res 121, 2849–2860 (2022). https://doi.org/10.1007/s00436-022-07628-y
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DOI: https://doi.org/10.1007/s00436-022-07628-y