Our study suggests that the combination of praziquantel and albendazole sulphoxide could potentially improve the current neurocysticercosis treatment.
Testera-Montes, Palomares, Jurado-Escobar, Rondon and Eguiluz-Gracia contributed equally to this work.
We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against Taenia cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts much slower and is less potent than PZQ.Several studies (3,8) have evaluated the effects of praziquantel (PZQ) and albendazole sulfoxide (ABZSO) against different species of metacestodes, but this study is the first to evaluate the minimum exposure times required for activity and the effective concentrations of PZQ and ABZSO against Taenia solium and Taenia crassiceps cysts.T. crassiceps cysts (ORF strain) were obtained from experimentally infected male BALB/c mice (age, 2 months). The mice were killed by cervical dislocation, and the metacestodes were removed from the peritoneal cavity. T. solium cysts were obtained from the skeletal muscle of naturally infected pigs. The parasites were washed with sterile 0.9% saline solution, and only those which exhibited an intact bladder surface were used for the experiments.Stock solutions of ABZSO and PZQ were prepared in dimethyl sulfoxide (DMSO) and ethanol, respectively. Working solutions of the drugs were prepared with culture medium to obtain PZQ concentrations from 0.001 to 0.3 g/ml and ABZSO concentrations from 0.0125 to 2.5 g/ml. Culture media containing 0.25% DMSO or 0.05% ethanol were prepared as controls. Each cell culture flask contained 25 cysts in 5 ml of culture medium and was incubated at 37°C with 5% CO 2 . The parasites were observed with an inverted light microscope (Reichert 569). The criteria used to assess cyst mortality in vitro were total paralysis of the membrane and cyst collapse. In order to determine the exposure time required for activity for PZQ, the cysts were observed each 15 min for 6 h; after this time, observations were made each 24 h for 11 days. For ABZSO, the parasites were observed each 24 h for 11 days. The culture medium was changed every day. Each experiment was performed in quadruplicate.The effective concentrations that killed 50 and 99% of the parasites (EC 50 s and EC 99 s, respectively) were determined at 4 and 6 h and 11 days for PZQ and at 11 days for ABZSO. Each experiment was performed in triplicate. Data were analyzed by logistic regression by using SPSS software (version 9.0).When the cysts were exposed to the drugs, an immediate contraction of the membrane was found; extensive vacuolization of the teguments and evagination were also observed. Figure 1A shows the loss of the cystic fluid of T. solium cysts after treatment with PZQ, and Fig. 1B shows the loss of the integrity of the membrane when the T. crassiceps cysts were exposed to the drugs.The maximum effects on T. crassiceps and T. solium cysts were observed after 4 and 6 h, respectively, when the concentrations of PZQ were in the range of 0.012 to 0.1 g/ml. When the effects of PZQ against T. crassiceps cysts were evaluated at lower concentrations (0...
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