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Palabras clave
terapia dirigida al huésped
activación de macrófagos
óxido nítrico
citocinas
cicatrización de heridas
productos naturales
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Resumen
Leishmania braziliensis, agente causal de la leishmaniasis cutánea (LC), sigue siendo un desafío importante de salud pública debido a la toxicidad, la eficacia variable y la resistencia emergente de las terapias sistémicas. Sin embargo, pese al creciente respaldo de las guías a tratamientos tópicos, son escasos los candidatos desarrollados. Evaluamos aquí los efectos antileishmaniales, inmunomoduladores y pro-regenerativos de una formulación tópica que combina saponinas triterpénicas de Sapindus saponaria (SS) y una hidrazona de cromano sintética (TC2), utilizando un modelo estandarizado de LC por L. braziliensis en hámsters. Los efectos antiparasitarios e inmunomoduladores de TC2SS se analizaron en macrófagos derivados de monocitos humanos infectados, evaluando carga parasitaria, morfología, producción de óxido nítrico (NO) y especies reactivas de oxígeno (ROS), y expresión de citocinas. La eficacia in vivo y las respuestas tempranas de cicatrización se valoraron en un modelo de piel dorsal de hámster tratado tópicamente con TC2SS al 4 % y se compararon con las de los antimoniales intralesionales, incluyendo la expresión del factor de crecimiento epidérmico (EGF) y el factor de crecimiento transformante β1 (TGFβ1). La TC2SS redujo la infección intracelular, disminuyó la carga parasitaria e indujo cambios morfológicos compatibles con la activación de macrófagos, preservando la producción de NO y ROS inducida por la infección y aumentando selectivamente el NO tardío. El análisis de citocinas mostró la supresión coordinada de IL1β, TNFα, IL4, IL10 y TGFβ1, así como la preservación de MIP1α. In vivo, la TC2SS alcanzó tasas de curación comparables a las de los antimoniales, con regresión uniforme de las lesiones, ausencia de fallos terapéuticos y sin toxicidad sistémica, además de incrementar la relación EGF/TGFβ1. En conjunto, la TC2SS aportó beneficios duales dirigidos al parásito y al huésped, lo que respalda su desarrollo como candidato terapéutico tópico para la LC por L. braziliensis.
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