RESUMO
Neurocysticercosis (NCC) is a public health issue in endemic regions and is considered the main preventable cause of neurologic disease. It is caused by the presence of Taenia solium cysticercus in the central nervous system. The current treatment is performed with anthelminthic drugs - albendazole (ABZ) or praziquantel - associated with anti-inflammatory and corticosteroids in order to prevent the negative effects of the inflammatory reaction to the parasite's death. Ivermectin (IVM) is an anthelminthic drug that has been shown to present an anti-inflammatory effect. The aim of this study was to was to evaluate the histopathologic aspects of experimental NCC after in vivo treatment with a combination of ABZ-IVM. Balb/c mice were intracranially inoculated with T. crassiceps cysticerci and after 30 days of infection were treated with a single dose of NaCl 0.9% (control group), ABZ monotherapy (40 mg/kg), IVM monotherapy (0.2 mg/kg) or a combination of ABZ-IVM. 24h after the treatment the animals were euthanized and the brain was removed for histopathologic analysis. The IVM monotherapy and ABZ-IVM combination showed more degenerated cysticerci, less inflammatory infiltration, meningitis and hyperemia than the other groups. Therefore, it is possible to recommend the combination of albendazole and ivermectin as alternative chemotherapy for NCC due to its antiparasitic and anti-inflammatory effects, with potential to decrease the negative effects of the inflammatory burst when the parasite is killed within the CNS.
Assuntos
Anti-Helmínticos , Neurocisticercose , Animais , Camundongos , Albendazol/farmacologia , Albendazol/uso terapêutico , Neurocisticercose/tratamento farmacológico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Anti-Helmínticos/farmacologia , Cysticercus , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
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.
Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Cysticercus/efeitos dos fármacos , Neurocisticercose/tratamento farmacológico , Animais , Cysticercus/fisiologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Neurocysticercosis is the most common parasitic infection of the nervous system and currently represents a serious public health issue in many regions of Latin America, Asia, and Africa. To date, praziquantel is one of the chosen drugs for the treatment of neurocysticercosis. Its mechanism of action is based on the inhibition of different biochemical pathways within the parasite which contribute to its death. Thus, the aim of this work was to analyze, for the first time, whether the nanoformulations of praziquantel would modify the energetic pathway of Taenia crassiceps cysticerci, after an intracranial inoculation in BALB/c mice. Praziquantel nanosuspensions were formulated with polyvinyl alcohol, poloxamer 188, and poloxamer 407, as stabilizers. These formulations exhibited particle size in a range of 74-285 nm and zeta potential values in a range of - 8.1/- 13.2 depending on the type of stabilizer. Physical stability study at both 4 ± 2 and 25 ± 2 °C indicated that praziquantel (PZQ) nanoparticles were stable in terms of solubility and particle size after 120-day storage. In vivo studies demonstrated that those nanosystems were able to produce significant modifications on the concentrations of oxaloacetate, citrate, pyruvate, alpha-ketoglutarate, malate, succinate, lactate, beta-hydroxybutyrate, fumarate, and propionate involved in the metabolism of Taenia crassiceps cysticerci. Therefore, these nanoformulations may be considered as a promising tool to deliver praziquantel to the brain for the effective management of neurocysticercosis.