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Partial inhibition of the main energetic pathways and its metabolic consequences after in vivo treatment with benzimidazole derivatives in experimental neurocysticercosis

Published online by Cambridge University Press:  31 July 2019

Guaraciara de Andrade Picanço
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Nayana Ferreira de Lima
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Taynara Cristina Gomes
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Carolina Miguel Fraga
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Daniella de Sousa Moreira Mendes Alves
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Rafael Castillo
Affiliation:
Chemistry Faculty, National Autonomous University of Mexico, Mexico City, Mexico
Tatiane Luiza da Costa
Affiliation:
Clinical Hospital, Federal University of Goias, Goiania, Brazil
Ruy de Souza Lino-Junior
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Javier Ambrosio
Affiliation:
Medicine Faculty, National Autonomous University of Mexico, Mexico City, Mexico
Marina Clare Vinaud*
Affiliation:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
*
Author for correspondence: Marina Clare Vinaud, E-mail: marinavinaud@gmail.com

Abstract

Benzimidazole derivatives such as albendazole (ABZ) and mebendazole are important molecules used in helminthic treatment. Neurocysticercosis is the main cause of acquired epilepsy throughout the world and is currently treated with ABZ. New molecules have been studied in order to aid in the treatment of this neglected tropical disease, among them RCB15 and RCB20. The aim of this study was to evaluate the metabolic impact of RCB15 and RCB20 on Taenia crassiceps cysticerci intracranially inoculated in Balb/c mice. Thirty days after the inoculation the mice were treated with 50 mg kg−1 of RCB15, RCB20, ABZ or NaCl 0.9%. The euthanasia and cysticerci removal were performed 24 h after the treatment. The cysticerci were analysed through high performance liquid chromatography. After the treatments, there was an impairment in the main energetic pathways such as glycolytic pathway, homolactic fermentation or in mitochondrion energy production detected through the decrease in pyruvate, lactate, oxaloacetate, malate and fumarate concentrations. This induced the parasite to resort to alternative energetic pathways such as proteins catabolism, propionate fermentation and fatty acids oxidation. Therefore, benzimidazole derivatives are a promising alternative to ABZ use as they also reach the brain tissue and induce a metabolic stress in the cysticerci.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2019 

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