LA MEDICINA TRADICIONAL Y EL REPOSICIONAMIENTO DE FÁRMACOS COMO ESTRATEGIAS TERAPÉUTICAS EN LEISHMANIASIS CUTÁNEA
Traditional medicine and drug repositioning as therapeutic strategies to treat cutaneous leishmaniasis
DOI:
https://doi.org/10.15446/abc.v30n1.112313Palabras clave:
Leishmaniasis del Nuevo Mundo, reposicionamiento de medicamentos, sinergismo farmacológico, terapéutica tradicional, termoterapia (es)new world cutaneous leishmaniasis, drug repositioning, drug synergism, traditional therapeutics, thermotherapy (en)
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Las opciones terapéuticas para los pacientes con leishmaniasis cutánea son pocas, de eficacia variable y tóxicas. La medicina tradicional (MT, popular o indígena) y el reposicionamiento de fármacos (utilización de fármacos de entidades diferentes) proveen alternativas de estudio. Se evaluaron en Leishmania (Leishmania) amazonensis sustancias como la miel de abejas, café, extracto de Cannabis sativa y el tetrahidrocannabinol (THC), el calor y algunos fármacos. La potencia se expresó en concentraciones inhibitorias o citotóxicas (CI50 o CC50) de promastigotes, amastigotes intracelulares, células THP-1 y la efectividad en la inhibición de las lesiones en ratones BALB/c tratados tópicamente con formulaciones tipo crema, gel y ungüento. Adicionalmente se evaluó el efecto del calor y la actividad antioxidante. Los compuestos antileishmania más potentes de mayor a menor fueron el nifurtimox, THC, celecoxib, SbIII, C. sativa, ribavirina, azitromicina y el tratamiento veterinario con CI50 entre 1,1 y 85,8 µg/mL. En amastigotes intracelulares, el nifurtimox, celecoxib y SbIII fueron activos. La interacción del SbIII y celecoxib fue indiferente, sin embargo, in vivo el ungüento combinado preparado con cera de abejas presentó reducción y reepitelización completa de la lesión. Individualmente estos fármacos al igual que la crema de café + ribavirina controlaron el crecimiento de las lesiones. Los promastigotes, amastigotes axénicos y células THP-1 fueron susceptibles a altas temperaturas y el café y el THC mostraron actividad antioxidante. Estudios complementarios orientados a mejorar la dosificación, formulación, determinación de permeabilidad, entre otros son recomendados.
Therapeutic options for patients with cutaneous leishmaniasis are few, of variable efficacy and toxic. Traditional medicine (TM, popular or indigenous) and drug repositioning (use of drugs from different entities) provide study alternatives. Substances such as honey, coffee, Cannabis sativa, tetrahydrocannabinol (THC), heat and some drugs were evaluated in Leishmania (Leishmania) amazonensis. Potency was expressed in inhibitory or cytotoxic concentrations (IC50 or CC50) of promastigotes, intracellular amastigotes, and THP-1 cells, and effectiveness in inhibiting lesions in BALB/c mice treated topically with cream, gel, and ointment-type formulations. Additionally, the effect of heat and antioxidant activity were evaluated. The most potent antileishmania compounds from highest to lowest were nifurtimox, THC, celecoxib, SbIII, C. sativa, ribavirin, azithromycin, and veterinary treatment with IC50 between 1.1 and 85.8 μg/mL. In intracellular amastigotes, nifurtimox, celecoxib and SbIII were active. The interaction of SbIII and celecoxib was indifferent; however, in vivo, the combined ointment prepared with beeswax showed reduction and complete re-epithelialization of the lesion. Individually, these drugs, as well as coffee cream + ribavirin, controlled the growth of lesions. Promastigotes, axenic amastigotes, and THP-1 cells were susceptible to high temperatures, and coffee and THC showed antioxidant activity. Further studies are recommended to improve dosage, formulation, and permeability determination, among other factors.
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