Evaluación del espectro y propiedades neutralizantes del Varespladib hacia fosfolipasas A2 tóxicas de venenos ofídicos
Fecha
2024
Tipo
tesis de maestría
Autores
Bryan Quirós, Wendy
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Resumen
El envenenamiento ofídico es un problema médico y de salud pública debido a su incidencia y al número de muertes que causa a nivel mundial. Las fosfolipasas A2 constituyen un porcentaje importante de los venenos de serpientes, y son las enzimas responsables de varios de los efectos en el organismo en el envenenamiento. A pesar de que se utilizan antivenenos eficientes, es necesario el desarrollo de nuevos tratamientos eficaces y económicos que logren disminuir los efectos del envenenamiento ofídico en el organismo. El Varespladib es un compuesto que ha mostrado características inhibitorias de las fosfolipasas A2 de los venenos de serpientes, y parece tener el potencial de ser desarrollado como un pretratamiento asequible ante el envenenamiento por mordeduras de serpiente. Con este estudio se buscó evaluar la capacidad del Varespladib para inhibir las actividades de fosfolipasas A2 representativas de los grupos I y II de venenos de serpientes, así como de sus correspondientes venenos completos. Para ello, se realizaron experimentos para determinar el efecto del Varespladib sobre la actividad enzimática, la citotoxicidad in vitro, y la miotoxicidad in vivo de cada una de estas toxinas y venenos completos. Los resultados mostraron una inhibición significativa de la toxicidad, apoyando el concepto de que el Varespladib pueda llegar a utilizarse como un tratamiento complementario eficaz que disminuya los efectos del envenenamiento ofídico causado por diversas especies de serpientes.
Snakebite envenoming is a medical and health problem due to its incidence and the number of deaths it causes worldwide. Phospholipases A2 constitute an important component of snake venoms and are the enzymes responsible for various effects in the organism in the envenoming. Although efficient antivenoms are available, it is still necessary to develop effective and economic complementary therapies capable of decreasing the effects of snake envenoming in the organism. Varespladib is a compound that has shown inhibitory properties toward phospholipases A2 of snake venoms and seems to have the potential to be developed as an affordable pretreatment against snakebite envenoming. This study aimed to evaluate the ability of Varespladib to inhibit the activities of phospholipases A2 representative of groups I and II of snake venoms, as well as their corresponding complete venoms. In order to achieve this, experiments were performed to determine the effect of Varespladib on enzymatic activity, myotoxicity, and cytotoxicity of each of these toxins and complete venoms. Results showed that a significant inhibition of toxicity was achieved, supporting the notion that Varespladib could be used in the future as an effective complementary therapy to decrease the effects of snakebite envenoming.
Snakebite envenoming is a medical and health problem due to its incidence and the number of deaths it causes worldwide. Phospholipases A2 constitute an important component of snake venoms and are the enzymes responsible for various effects in the organism in the envenoming. Although efficient antivenoms are available, it is still necessary to develop effective and economic complementary therapies capable of decreasing the effects of snake envenoming in the organism. Varespladib is a compound that has shown inhibitory properties toward phospholipases A2 of snake venoms and seems to have the potential to be developed as an affordable pretreatment against snakebite envenoming. This study aimed to evaluate the ability of Varespladib to inhibit the activities of phospholipases A2 representative of groups I and II of snake venoms, as well as their corresponding complete venoms. In order to achieve this, experiments were performed to determine the effect of Varespladib on enzymatic activity, myotoxicity, and cytotoxicity of each of these toxins and complete venoms. Results showed that a significant inhibition of toxicity was achieved, supporting the notion that Varespladib could be used in the future as an effective complementary therapy to decrease the effects of snakebite envenoming.
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Palabras clave
Veneno, Salud pública, Serpientes