Evaluation of the mechanism of action of albendazole on adult rat lungworm (Angiostrongylus cantonensis)

Jacob, John; Siraj, Md Afjalus; Steel, Argon; Tan, Ghee Teng; Jarvi, Susan I.

doi:10.1016/j.exppara.2022.108355

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Many other studies have also explored how to enhance the efficacy of Albendazole in deworming (56, 57). Albendazole sulphoxide binds to parasite ßmicrotubules, preventing them from aggregating into microtubules to disrupt the cascade of mid-stage cell division and ultimately leading to the death of individual cells and then the death of the parasite (58), Albendazole sulphoxide can also inhibit the glucose absorption of the parasite, leading to glycogen depletion, or inhibit the fumarate reductase system, blocking the production of ATP and therefore making it impossible for the parasite to survive and reproduce (59). However, Albendazole has low solubility in water and drug concentration in hydatid lesions (60), and different from Ubenimex, it has little inhibitory effect on hydatid infiltrative growth and invasion.…”

Section: Discussionmentioning

confidence: 99%

Ubenimex combined with Albendazole for the treatment of Echinococcus multilocularis-induced alveolar echinococcosis in mice

Zhou,

Huayu,

et al. 2024

Front. Vet. Sci.

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IntroductionAlveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis-Leucine aminopeptidase (EM-LAP) could inhibit the growth and invasion of E. multilocularis in host liver, and Ubenimex, a broad-spectrum inhibitor of LAP, could also inhibit E. multilocularis invasion but had a limited effect on the growth and development of E. multilocularis.MethodsIn this study, the therapeutic effect of Ubenimex combined with Albendazole on AE was evaluated. Mice were intraperitoneally injected with protoscoleces and imaging examination was performed at week 8 and week 16 to detect cyst change. During this period, mice were intraperitoneally injected with Ubenimex and intragastrically administered with Albendazole suspension. At last, the therapeutic effect was evaluated by morphological and pathological examination and liver function.ResultsThe results revealed that the combined treatment could inhibit the growth and infiltration of cysts in BALB/c mice infected with E. multilocularis protoscoleces. The weight, number, invasion and fibrosis of cysts were reduced in mice treated with Ubenimex in combination with Albendazole. The same effect was achieved by the single Ubenimex treatment because of its inhibitory effect on LAP activity, but it was less effective in inhibiting the growth of cysts. The levels of ALT, AST, TBIL, DBIL, ALP, and γ-GT were reduced after the combined treatment, indicating that treatment with both Ubenimex and Albendazole could alleviate liver damage.DiscussionThis study suggests that the combined treatment with Ubenimex and Albendazole could be a potential therapeutic strategy for E. multilocularis infections.

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Section: Discussionmentioning

confidence: 99%

Ubenimex combined with Albendazole for the treatment of Echinococcus multilocularis-induced alveolar echinococcosis in mice

Zhou,

Huayu,

et al. 2024

Front. Vet. Sci.

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“…El Albendazol se une al sitio de unión de la colchicina de la tubulina inhibiendo así la polimerización de los microtúbulos. De esta manera, la ausencia de microtúbulos afectan la captación de glucosa por parte del parásito, llevando a la muerte del mismo (Jacob et al, 2022).…”

Section: Manifestaciones Clínicasunclassified

Búsqueda de nuevos fármacos antihelmínticos basada en el análisis estructura-función de proteínas que unen ácidos grasos (FABPs) de cestodos mediante técnicas bioinformáticas y quimioinformáticas

Rodríguez

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La equinococosis y la cisticercosis se encuentran dentro de las Enfermedades Tropicales Desatendidas (ETDs) definidas por la Organización Mundial de la Salud (OMS), afectando a poblaciones pertenecientes a áreas tropicales y subtropicales. Echinococcus granulosus y Echinococcus multilocularis son los agentes etiológicos de la equinococosis quística y alveolar, respectivamente, mientras que Taenia solium es el parásito causante de la cisticercosis. En general, los parásitos cestodos presentan un metabolismo lipídico deficiente debido a la carencia de varias enzimas asociadas a la biosíntesis. Esta situación hace que deban incorporar a los lípidos desde el hospedador. En este sentido, las FABPs (del inglés Fatty Acid Binding Proteins) han sido postuladas como esenciales para el ciclo de vida de los cestodes, por su relevancia en el tráfico e incorporación de lípidos. En la presente tesis doctoral se han desarrollado modelos computacionales para descubrir inhibidores que pudieran afectar la incorporación de lípidos en los parásitos E. granulosus, E. multilocularis y T. solium, a partir de bases de datos de compuestos químicos. Para tales propósitos, se ha hecho uso de la estrategia de cribado virtual en paralelo (CVP), utilizando modelos basados en descriptores moleculares obtenidos a través de métodos indirectos (basado en ligandos), como así también modelos de docking molecular utilizando las estructuras tridimensionales de las distintas isoformas de las FABPs de dichos parásitos, la gran mayoría de ellas obtenidas mediante modelado por aprendizaje automático y dinámica molecular (DM). Esta tesis doctoral permitió la identificación de cuatro compuestos candidatos para el tratamiento de las diferentes variantes de la equinococosis, como así también para la cisticercosis, en donde se evidenció interacción entre las moléculas propuestas y las FABPs de cestodes de manera experimental. Por otra parte, las estrategias de cribado in silico tuvieron gran importancia para encontrar nuevas terapéuticas contra las ETDs, en donde la inversión de tiempo y dinero para la identificación de un compuesto de unión a nuestro blanco molecular fue poca en comparación al desarrollo de un fármaco nuevo, un aspecto clave en este tipo de enfermedades, en donde la inversión privada ha sido históricamente muy baja.

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Management of Rat Lungworm Disease (Neuroangiostrongyliasis) Using Anthelmintics: Recent Updates and Recommendations

et al. 2022

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While there have been legitimate concerns in the past regarding the use of anthelmintics for the management of neuroangiostrongyliasis (rat lungworm disease), recent studies demonstrate that they can be considered safe and efficacious, particularly albendazole, which is regarded as the choice anthelmintic for its management. However, physician hesitancy to prescribe, as well as problems of availability persist, at least in Hawaii, which is considered the epicenter of this disease in the US. As a result, many patients suffer a diminished quality of life or even death. Here, we discuss recent studies that provide insights into new treatments and preventative interventions, which can be more rigorously used for the management of neuroangiostrongyliasis. In summary, results from recent studies suggest that albendazole and avermectins are beneficial for post-exposure management, pyrantel pamoate is beneficial as a post-exposure prophylactic, and levamisole is deserving of further study for the treatment of neuroangiostrongyliasis.

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Evaluation of the mechanism of action of albendazole on adult rat lungworm (Angiostrongylus cantonensis)

Cited by 3 publications

References 29 publications

Ubenimex combined with Albendazole for the treatment of Echinococcus multilocularis-induced alveolar echinococcosis in mice

Ubenimex combined with Albendazole for the treatment of Echinococcus multilocularis-induced alveolar echinococcosis in mice

Búsqueda de nuevos fármacos antihelmínticos basada en el análisis estructura-función de proteínas que unen ácidos grasos (FABPs) de cestodos mediante técnicas bioinformáticas y quimioinformáticas

Management of Rat Lungworm Disease (Neuroangiostrongyliasis) Using Anthelmintics: Recent Updates and Recommendations

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