Efecto de la combinación de Anfotericina-B y fármacos tricíclicos frente a promastigotes de Leishmania braziliensis
The treatment of cutaneous leishmaniasis caused by Leishmania amazonensis and Leishmania braziliensis remains challenging due to drug toxicity, cost, and the emergence of resistant strains. Amphotericin B (AmB), in its various formulations, represents a relevant therapeutic alternative, but its...
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| Autores principales: | , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2025
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/50594 |
| Aporte de: |
| Sumario: | The treatment of cutaneous leishmaniasis caused by Leishmania amazonensis and Leishmania braziliensis remains challenging due to drug toxicity, cost, and the emergence of resistant strains. Amphotericin B (AmB), in its various formulations, represents a relevant therapeutic alternative, but its efficacy and tolerability vary by species and clinical context. In this regard, the combination of drugs with different mechanisms of action has emerged as a promising strategy. AmB exerts its effect by binding to ergosterol in the parasite membrane, while clomipramine (Clo) and thioridazine (Thio), clinically used psychotropic drugs, have been shown to inhibit, at subtherapeutic concentrations, trypanothione reductase—a peroxide-reducing enzyme specific to the parasite. The aim of this study was to evaluate the in vitro effect of combined AmB-Clo and AmB-Thio therapy on L. braziliensis promastigotes.
Promastigotes (3 × 10⁶/mL) were incubated with individual and combined drug concentrations (AmB = 0.02–0.62 μg/mL; Clo/Thio = 0.8–15 μg/mL). After 72 hours, parasite counts were performed, and the 50% inhibitory concentration (IC₅₀) and the Combination Index (CI; CI > 1 = antagonistic, CI = 1 = additive, CI < 1 = synergistic) were determined. An isobologram was then constructed using the IC₅₀ values of each drug and their combinations.
In the AmB-Clo assay, the IC₅₀ values for individual drugs were: AmB = 0.09 μg/mL and Clo = 8.96 μg/mL. Combinations with Clo yielded CI values of 2.4, 1.87, 1.43, 1.32, and 1.22, all above the additivity line in the isobologram, indicating antagonism. Similar results were observed in the AmB-Thio assays, where the IC₅₀ values for individual drugs were: AmB = 0.38 μg/mL and Thio = 7.8 μg/mL, while CI values were 2.34, 1.5, 1.31, 1.61, and 1.87—all antagonistic.
These results indicate that the susceptibility of L. braziliensis to AmB was not enhanced by combination with the tricyclic drugs, showing an opposite effect to that previously observed in studies involving L. amazonensis. These differences may be attributed to the biological, clinical, and immunological particularities of each species, which significantly influence their susceptibility to different therapeutic agents.
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