Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis
Abstract: Leishmaniasis is a disease caused by parasites of the Leishmania genus. Amphotericin-B (Anf) is one of the main drugs used for its treatment, however cases of toxicity and resistance have been reported. The search for new therapies involves the use of drug combinations, which hav...
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/35035 |
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I10-R327-article-35035 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
Leishmania amazonensis combination therapy amphotericin-B clomipramine Leishmania amazonensis terapia combinada anfotericina-B clomipramina |
| spellingShingle |
Leishmania amazonensis combination therapy amphotericin-B clomipramine Leishmania amazonensis terapia combinada anfotericina-B clomipramina Barrionuevo , CN Dimmer , JA Konigheim , BS Aguilar , JJ Rivarola , HW Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| topic_facet |
Leishmania amazonensis combination therapy amphotericin-B clomipramine Leishmania amazonensis terapia combinada anfotericina-B clomipramina |
| author |
Barrionuevo , CN Dimmer , JA Konigheim , BS Aguilar , JJ Rivarola , HW |
| author_facet |
Barrionuevo , CN Dimmer , JA Konigheim , BS Aguilar , JJ Rivarola , HW |
| author_sort |
Barrionuevo , CN |
| title |
Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| title_short |
Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| title_full |
Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| title_fullStr |
Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| title_full_unstemmed |
Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis |
| title_sort |
combined therapy “in vitro" of amphotericin-b and clomipramine on promastigotes of leishmania amazonensis |
| description |
Abstract:
Leishmaniasis is a disease caused by parasites of the Leishmania genus. Amphotericin-B (Anf) is one of the main drugs used for its treatment, however cases of toxicity and resistance have been reported. The search for new therapies involves the use of drug combinations, which have been shown to be effective for conditions of similar host-pathogen biology and the identification of molecular targets present in the parasite, but absent in the host, such as trypanethione reductase in Leishmania. An inhibitor drug of this enzyme is clomipramine (Clo), traditionally used for its antidepressant action. The objective of this work was to analyze the combined therapy "in vitro" of Anf and Clo on promastigotes of L. amazonensis.
Were incubated 5x106 promastigotes / mL with concentrations of the drugs alone and in combination (Anf = 0.02-0.62 μg / mL and Clo = 0.48-7.8 μg / mL). These concentrations were previously shown to be non-cytotoxic in Vero (CV) cells. After 72 h, the parasite count was performed and the 50% inhibitory concentration (IC50) and the Combination Index (IC: IC> 1 antagonistic; IC = 1 additive; IC <1 synergistic) were determined. Finally, the isobologram corresponding to the IC50 values of each of the drugs and their combinations was performed.
The IC50 values of each drug were: Anf = 0.18 µg / ml and Clo = 6 µg / ml, being 103 and 21 times lower than the cytotoxic concentration in CV. Of the concentrations studied, the combination of Clo (0.48-7.8 μg / mL) with 0.02; 0.04 and 0.08 of Anf were located below the additivity line, which indicates a synergistic effect, coinciding with the value obtained from CI = 0.61.
These tests show an increase in the antiparasitic effect at low concentrations when using combined therapies, allowing to reduce the toxic effects on the host. The synergistic effect observed is consistent with the results found in previous studies in Trypanosoma cruzi and L. braziliensis. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2021 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/35035 |
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2024-09-03T21:03:01Z |
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2024-09-03T21:03:01Z |
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I10-R327-article-350352024-04-15T16:19:09Z Combined therapy “in vitro" of Amphotericin-B and Clomipramine on promastigotes of Leishmania amazonensis Terapia combinada “in vitro” de Anfotericina-B y Clomipramina sobre promastigotes de Leishmania amazonensis Barrionuevo , CN Dimmer , JA Konigheim , BS Aguilar , JJ Rivarola , HW Leishmania amazonensis combination therapy amphotericin-B clomipramine Leishmania amazonensis terapia combinada anfotericina-B clomipramina Abstract: Leishmaniasis is a disease caused by parasites of the Leishmania genus. Amphotericin-B (Anf) is one of the main drugs used for its treatment, however cases of toxicity and resistance have been reported. The search for new therapies involves the use of drug combinations, which have been shown to be effective for conditions of similar host-pathogen biology and the identification of molecular targets present in the parasite, but absent in the host, such as trypanethione reductase in Leishmania. An inhibitor drug of this enzyme is clomipramine (Clo), traditionally used for its antidepressant action. The objective of this work was to analyze the combined therapy "in vitro" of Anf and Clo on promastigotes of L. amazonensis. Were incubated 5x106 promastigotes / mL with concentrations of the drugs alone and in combination (Anf = 0.02-0.62 μg / mL and Clo = 0.48-7.8 μg / mL). These concentrations were previously shown to be non-cytotoxic in Vero (CV) cells. After 72 h, the parasite count was performed and the 50% inhibitory concentration (IC50) and the Combination Index (IC: IC> 1 antagonistic; IC = 1 additive; IC <1 synergistic) were determined. Finally, the isobologram corresponding to the IC50 values of each of the drugs and their combinations was performed. The IC50 values of each drug were: Anf = 0.18 µg / ml and Clo = 6 µg / ml, being 103 and 21 times lower than the cytotoxic concentration in CV. Of the concentrations studied, the combination of Clo (0.48-7.8 μg / mL) with 0.02; 0.04 and 0.08 of Anf were located below the additivity line, which indicates a synergistic effect, coinciding with the value obtained from CI = 0.61. These tests show an increase in the antiparasitic effect at low concentrations when using combined therapies, allowing to reduce the toxic effects on the host. The synergistic effect observed is consistent with the results found in previous studies in Trypanosoma cruzi and L. braziliensis. Resumen: La leishmaniasis es una enfermedad producida por parásitos del género Leishmania. Anfotericina-B (Anf) es uno de los principales fármacos utilizados para su tratamiento, sin embargo, se han reportado casos de toxicidad y resistencia. La búsqueda de nuevas terapias involucra la utilización de combinaciones de fármacos, que han demostrado ser efectivos para afecciones de similar biología patógeno-huésped y la identificación de blancos moleculares presentes en el parásito, pero ausentes en el huésped, como lo es la tripanotiona reductasa en Leishmania. Un fármaco inhibidor de esta enzima, es la clomipramina (Clo), empleado tradicionalmente por su acción antidepresiva. El objetivo de este trabajo fue analizar la terapia combinada “in vitro” de Anf y Clo sobre promastigotes de L. amazonensis. Se incubaron 5x106 promastigotes/mL con concentraciones de los fármacos solos y combinados (Anf=0,02-0,62 μg/mL y Clo=0,48-7,8 μg/mL). Previamente, se demostró que estas concentraciones no fueron citotóxicas en células Vero (CV). Luego de 72 h, se realizó el recuento de parásitos y se determinó la concentración inhibitoria del 50% (CI50) y el Índice de Combinación (IC: IC>1 antagónico; IC=1 aditivo; IC<1 sinérgico). Por último, se realizó el isobolograma correspondiente a los valores de CI50 de cada uno de los fármacos y de sus combinaciones. Los valores de CI50 de cada fármaco fueron: Anf=0,18 μg/mL y Clo=6 μg/mL, siendo 103 y 21 veces menor que la concentración citotóxica en CV. De las concentraciones estudiadas, la combinación de Clo (0,48-7,8 μg/mL) con 0,02; 0,04 y 0,08 de Anf se ubicaron por debajo de la línea de aditividad, lo que indica un efecto sinérgico, coincidente con el valor obtenido de IC=0,61. Estos ensayos evidencian un aumento en el efecto antiparasitario a bajas concentraciones al emplear terapias combinadas, permitiendo reducir los efectos tóxicos sobre el huésped. El efecto sinérgico observado es coincidente con los resultados hallados en estudios previos en Trypanosoma cruzi y L. braziliensis. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/35035 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |