Partial inhibition of the main energetic pathways and its metabolic consequences after in vivo treatment with benzimidazole derivatives in experimental neurocysticercosis
Por:
Picanço G.D.A., de Lima, Nayana Ferreira, Gomes, Taynara Cristina, Fraga, Carolina Miguel, Alves D.D.S.M.M., Castillo, Rafael, Da Costa T.L., Lino-Junior R.D.S., Ambrosio, Javier, Vinaud, Marina Clare
Publicada:
1 ene 2019
Resumen:
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. © 2019 Cambridge University Press.
Filiaciones:
Picanço G.D.A.:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
de Lima, Nayana Ferreira:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Univ Fed Goias, Trop Pathol & Publ Hlth Inst, Goiania, Go, Brazil
Gomes, Taynara Cristina:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Univ Fed Goias, Trop Pathol & Publ Hlth Inst, Goiania, Go, Brazil
Fraga, Carolina Miguel:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Univ Fed Goias, Trop Pathol & Publ Hlth Inst, Goiania, Go, Brazil
Alves D.D.S.M.M.:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Castillo, Rafael:
Chemistry Faculty, National Autonomous University of Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Chem Fac, Mexico City, DF, Mexico
Da Costa T.L.:
Clinical Hospital, Federal University of Goias, Goiania, Brazil
Lino-Junior R.D.S.:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Ambrosio, Javier:
Medicine Faculty, National Autonomous University of Mexico, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Med Fac, Mexico City, DF, Mexico
Vinaud, Marina Clare:
Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil
Univ Fed Goias, Trop Pathol & Publ Hlth Inst, Goiania, Go, Brazil
Univ Fed Goias, Clin Hosp, Goiania, Go, Brazil
|