Taenia crassiceps: Host treatment alters glycolisis and tricarboxilic acid cycle in cysticerci

Abstract

Human cysticercosis by Taenia crassiceps is rare although it is considered of zoonotic risk, especially to immunocompromised individuals. Albendazole and praziquantel are widely used and effective in its treatment. Their active forms inhibit the glucose uptake by the parasite and induce muscle contractions that alter its glycogen levels interfering in the energetic metabolism of the parasite and leading to its death. The aim of this study was to evaluate alterations in glycolysis, the tricarboxylic acid cycle and glucose concentrations caused by low dosage treatments of the hosts with albendazole and praziquantel. Therefore, T. crassiceps intraperitoneally infected mice were treated by gavage feeding with 5.75 or 11.5 mg/kg of albendazole and 3.83 or 7.67 mg/kg of praziquantel. The treated mice were euthanized after 24 h and the cysticerci collected were morphologically classified into initial, larval or final phases. Concentrations of the organic acid produced and glucose were evaluated to detect alterations into the glycolysis and the tricarboxylic acid cycle pathways through chromatography and spectrophotometry. The low dosage treatment caused a partial blockage of the glucose uptake by the cysticerci in spite of the non significant difference between its concentrations. An activation of the tricarboxylic acid cycle was noted in the cysticerci that received the treatment due to an increase in the production of citrate, malate and α-ketoglutarate and the consumption of oxaloacetate, succinate and fumarate. The detection of α-ketoglutarate indicates that the cysticerci which were exposed to the drugs after host treatment present different metabolic pathways than the ones previously described after in vitro treatment.

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

“…The T. crassiceps cysticerci are maintained in the animal's facilities of the Tropical Pathology and Public Health Institute of the Federal University of Goias since 2002, as described previously (Vaz et al ., 1997; Fraga et al ., 2012).…”

“…The organic acids were extracted from the cysticerci according to the previous description (Fraga et al ., 2012). Briefly, the cysticerci were defrosted and homogenized in 500 µ L of tris-HCl 0.1 M buffer supplemented with a protease inhibitor (SigmaFast protease inhibitor cocktail tablets, EDTA-free, Sigma ® ), pH 7.6.…”

Alternative energy production pathways in Taenia crassiceps cysticerci in vitro exposed to a benzimidazole derivative (RCB20)

“…The results were analysed through the Star Chromatography Workstation software (Agilent ® ), previously calibrated for the following organic acids identification: acetate, acetoacetate, β-hydroxybutyrate, propionate and fumarate (Vinaud et al 2007). The analysis of the proteins catabolism was performed through the quantification of urea, creatinin and total proteins in the culture medium which was performed through an Architec C8000 Plus device, using a commercial kit protocol and enzymatic method (Fraga et al 2012 b ).…”

“…The parasite removes from the environment or from reserve vacuoles the substrates for these pathways with considerable ATP production. In situations of environmental stress such as the presence of antihelminthic drugs that impair the glucose uptake the parasite enhances these metabolic pathways enabling its survival (Vinaud et al 2009; Fraga et al 2012 b ). Therefore the studies of the metabolic range of the parasites when exposed to drugs may indicate the pathways used to escape metabolic distress and a possible resistance development (Barot et al 2013).…”

Unusual cases of Taenia crassiceps cysticercosis in naturally infected animals in the Czech Republic

“…Experiments in mice showed a significant reduction of cysticerci after prolonged 20-and 25-day administration of albendazole (Zurabian et al 2013). In human medicine, the synergistic action of praziquantel and albendazole was employed to successfully treat infection (Garcia et al 2011;Fraga et al 2012;Anikpeh et al 2014). As for regular deworming of dogs, it is not effective against T. crassiceps cysticercosis, but may help to prevent contamination of the environment by tapeworm eggs contained in faeces of dogs parasitised by adult tapeworms in the intestine.…”