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1.
Acta Trop ; 221: 106027, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34216560

ABSTRACT

Cysticercosis is the presence of Taenia solium larval stage in tissues such as central nervous system, skin, muscles and eye globe. The current treatment is based on albendazole and praziquantel which already present resistance reports. Therefore, the search for alternative treatments is paramount. The aim of this study was to determine the effect of flubendazole and nitazoxanide on cytoskeleton proteins from Taenia crassiceps cysticerci, an experimental model for cysticercosis. Cysticerci were cultured in RPMI supplemented medium containing nitazoxanide and/or flubendazole. 24 h after the exposure the cysticerci were processed for scanning and transmission electron microscopy and for protein analysis of the cytoskeleton. The proteins were detected through 1D electrophoresis and identified through Western Blot. Nitazoxanide exposure increased tubulin and actin quantifications in T. crassiceps cysticerci. While flubendazole alone and the drugs combinations induced an increase in α-tubulin and actin and decreased ß-tubulin quantifications in the parasite. Morphological changes such as swelling and rupture of vesicle, stiff membrane, decrease in movements were observed when the cysticerci were incubated with the different compounds. In conclusion the drugs induced significative impact in the parasite`s cytoskeleton and may be considered as alternative treatments for cysticercosis.


Subject(s)
Cytoskeleton/drug effects , Mebendazole/analogs & derivatives , Nitro Compounds/pharmacology , Taenia , Thiazoles/pharmacology , Animals , Cysticercosis , Cysticercus/drug effects , Female , Mebendazole/pharmacology , Mice , Mice, Inbred BALB C , Taenia/drug effects
2.
BMC Infect Dis ; 20(1): 220, 2020 Mar 14.
Article in English | MEDLINE | ID: mdl-32171260

ABSTRACT

BACKGROUND: The management of disseminated cysticercosis is unclear and largely considered hazardous. The role of albendazole remains controversial in such patients. METHODS: A tertiary care, University hospital-based prospective intervention study was conducted from December 2015 to December 2017. Patients with disseminated cysticercosis, defined as the presence of multiple viable neurocysticerci (≥ 3) in the brain along with involvement of an additional extra site, were included in the study. Patients with cysticercal encephalitis were excluded. A detailed evaluation, including ophthalmoscopy, ocular B scans, ultrasound abdomen, and X-rays were done. Albendazole was administered at a dose of 15 mg/kg/day in 3 cycles of 28 days each. All patients were also given adjuvant corticosteroids and anti-epileptic drugs. Clinical and radiological follow up was carried out at a difference of 3 months between each treatment cycle. For radiological quantification, lesions were counted at 10 pre-specified levels. Statistical analysis was done to estimate the difference in seizure frequency and lesion load. RESULTS: Twenty-nine patients (21 with > 20 lesions; 8 with ≤ 20 lesions) were given albendazole as per the protocol. There was a significant reduction in the occurrence of seizures (P < 0.001) and headache (P < 0.001). A significant reduction in lesion load from baseline to third follow-up was seen in the estimations done at different levels (P < 0.001). No patient developed serious side-effect warranting cessation of therapy. CONCLUSION: Cyclical use of albendazole appears efficacious in treating disseminated cysticercosis. The method of quantification described may be used in future studies for objective assessment. TRIAL REGISTRATION: ISRCTN11630542; 28th September 2019; Retrospectively registered.


Subject(s)
Albendazole/administration & dosage , Albendazole/therapeutic use , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Cysticercus/drug effects , Neurocysticercosis/drug therapy , Parasite Load , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Animals , Anticonvulsants/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Child , Drug Therapy, Combination , Female , Follow-Up Studies , Headache , Humans , Male , Middle Aged , Neurocysticercosis/diagnostic imaging , Neurocysticercosis/parasitology , Prospective Studies , Radiography , Seizures , Treatment Outcome , Young Adult
3.
Acta Trop ; 202: 105254, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31689380

ABSTRACT

The benzimidazole derivative, 6-chloro-5-(2,3-dichlorophenoxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB15), has a similar mode of action and efficacy as albendazole, a commonly used anthelminthic drugs. The aim of this study was to evaluate its influence on the tricarboxylic acid cycle in Taenia crassiceps cysticerci. The parasites were cultured in supplemented RPMI medium containing albendazole sulfoxide (ABZSO) or RCB15, for 24 h. Then, frozen in liquid nitrogen for organic metabolites extraction. Samples were analyzed by high performance liquid chromatography and organic acids of the tricarboxylic acid cycle were detected. It was possible to observe changes in the concentrations of all acids involved in this metabolic pathway, with the exception of α-ketoglutarate, which was not detected in the control group neither in most of the treated groups. It indicates that the parasite presented a partial inhibition of the tricarboxylic acid cycle. The significant increase in the concentration of citrate, oxaloacetate and succinate in the RCB15 treated groups may indicate an activation of the fumarate reductase pathway, leading to metabolic distress. Therefore RCB15 may be considered an alternative for the treatment of tissue parasitic diseases, since it induced changes in the main metabolic pathway of the parasite.


Subject(s)
Anthelmintics/pharmacology , Benzimidazoles/pharmacology , Citric Acid Cycle/drug effects , Cysticercus/drug effects , Taenia/drug effects , Animals , Cysticercus/metabolism , Metabolic Networks and Pathways/drug effects , Mice, Inbred BALB C , Taenia/metabolism
4.
Exp Parasitol ; 208: 107792, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31707003

ABSTRACT

Nitazoxanide (NTZ) is a broad-spectrum drug used in intestinal infections, but still poorly explored in the treatment of parasitic tissular infections. This study aimed to evaluate the in vitro responses of the energetic metabolism of T. crassiceps cysticerci induced by NTZ. The organic acids of the tricarboxylic acid cycle, products derived from fatty acids oxidation and protein catabolism were analyzed. These acids were quantified after 24 h of in vitro exposure to different NTZ concentrations. A positive control group was performed with albendazole sulfoxide (ABZSO). The significant alterations in citrate, fumarate and malate concentrations showed the NTZ influence in the tricarboxylic acid (TCA) cycle. The non-detection of acetate confirmed that the main mode of action of NTZ is effective against T. crassiceps cysticerci. The statistical differences in fumarate, urea and beta-hydroxybutyrate concentrations showed the NTZ effect on protein catabolism and fatty acid oxidation. Therefore, the main energetic pathways such as the TCA cycle, protein catabolism and fatty acids oxidation were altered after in vitro NTZ exposure. In conclusion, NTZ induced a significant metabolic stress in the parasite indicating that it may be used as an alternative therapeutic choice for cysticercosis treatment. The use of metabolic approaches to establish comparisons between anti parasitic drugs mode of actions is proposed.


Subject(s)
Antiparasitic Agents/pharmacology , Taenia/drug effects , Thiazoles/pharmacology , Albendazole/analogs & derivatives , Albendazole/pharmacology , Analysis of Variance , Animals , Anthelmintics/pharmacology , Citrates/metabolism , Citric Acid Cycle/drug effects , Culture Media/chemistry , Cysticercus/drug effects , Cysticercus/metabolism , Energy Metabolism/drug effects , Fumarates/metabolism , Ketoglutaric Acids/metabolism , Malates/metabolism , Neurocysticercosis/drug therapy , Nitro Compounds , Oxaloacetic Acid/metabolism , Succinic Acid/metabolism , Taenia/metabolism
5.
Parasitology ; 146(12): 1578-1582, 2019 10.
Article in English | MEDLINE | ID: mdl-31303189

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.


Subject(s)
Anthelmintics/pharmacology , Benzimidazoles/pharmacology , Cysticercus/drug effects , Neurocysticercosis/drug therapy , Animals , Cysticercus/physiology , Energy Metabolism/drug effects , Female , Mice , Mice, Inbred BALB C
6.
J Helminthol ; 93(5): 539-547, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30149822

ABSTRACT

Androgens have been shown to exert a cysticidal effect upon Taenia crassiceps, an experimental model of cysticercosis. To further inquire into this matter, the Taenia crassiceps model was used to evaluate the expression of several proteins after testosterone (T4) and dihydrotestosterone (DHT) in vitro treatment. Under 2-D proteomic maps, parasite extracts were resolved into approximately 130 proteins distributed in a molecular weight range of 10-250 kDa and isoelectrical point range of 3-10. The resultant proteomic pattern was analysed, and significant changes were observed in response to T4 and DHT. Based on our experience with electrophoretic patterns and proteomic maps of cytoskeletal proteins, alteration in the expression of isoforms of actin, tubulin and paramyosin and of other proteins was assessed. Considering that androgens may exert their biological activity in taeniids through the non-specific progesterone receptor membrane component (PGRMC), we harnessed bioinformatics to propose the identity of androgen-regulated proteins and establish their hypothetical physiological role in the parasites. These analyses yield a possible explanation of how androgens exert their cysticidal effects through changes in the expression of proteins involved in cytoskeletal rearrangement, dynamic vesicular traffic and transduction of intracellular signals.


Subject(s)
Androgens/pharmacology , Cell Death , Proteome , Taenia/drug effects , Taenia/physiology , Actins/genetics , Animals , Computational Biology , Cysticercosis/pathology , Cysticercus/drug effects , Cysticercus/physiology , Cytoskeleton/drug effects , Cytoskeleton/genetics , Dihydrotestosterone/pharmacology , Female , Mice , Mice, Inbred BALB C , Receptors, Progesterone/genetics , Testosterone/pharmacology , Tropomyosin/genetics , Tubulin/genetics
7.
Acta Trop ; 190: 361-364, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30553893

ABSTRACT

Neurocysticercosis is the most frequent helminthiasis of the central nervous system and is caused by the presence of Taenia solium cysticerci. Nitazoxanide (NTZ) is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antiprotozoal activity due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme which is essential to anaerobic energy metabolism. The aim of this work was to determine the effect of NTZ on the energetic metabolism of Taenia crassiceps cysticerci intracranially inoculated BALB /c mice. The infected animals were treated with a single oral dose of NTZ 30 days after the inoculation. Analysis of the organic acids was performed through high performance liquid chromatography. Glucose was detected only in the treated groups, alongside with a significant decrease in lactate, pyruvate and oxaloacetate concentrations which indicate an increase in gluconeogenesis. The non-detection of alpha-ketoglutarate indicated the use of the fumarate reductase pathway in all groups. It was possible to confirm the drugs mode of action due to the non-detection of acetate in the treated groups. There was an increase in the fatty acids oxidation. Therefore it was possible to observe that NTZ induces gluconeogenesis as well as the increase of alternative energetic pathways such as fatty acids oxidation in T. crassiceps cysticerci.


Subject(s)
Anthelmintics/pharmacology , Cysticercus/metabolism , Gluconeogenesis/drug effects , Neurocysticercosis/metabolism , Taenia/metabolism , Thiazoles/pharmacology , Administration, Oral , Animals , Anthelmintics/therapeutic use , Chromatography, High Pressure Liquid , Cysticercus/drug effects , Energy Metabolism/drug effects , Fatty Acids/metabolism , Glucose/metabolism , Lactic Acid/metabolism , Metabolic Networks and Pathways/drug effects , Mice , Mice, Inbred BALB C , Neurocysticercosis/drug therapy , Nitro Compounds , Oxaloacetic Acid/metabolism , Oxidation-Reduction , Pyruvic Acid/metabolism , Taenia/drug effects , Thiazoles/therapeutic use
8.
Drug Deliv Transl Res ; 8(5): 1265-1273, 2018 10.
Article in English | MEDLINE | ID: mdl-30117119

ABSTRACT

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.


Subject(s)
Anthelmintics/administration & dosage , Metabolome/drug effects , Neurocysticercosis/drug therapy , Praziquantel/administration & dosage , Animals , Anthelmintics/chemistry , Anthelmintics/therapeutic use , Cysticercus/drug effects , Cysticercus/physiology , Disease Models, Animal , Drug Stability , Metabolomics/methods , Mice , Mice, Inbred BALB C , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Neurocysticercosis/metabolism , Particle Size , Praziquantel/chemistry , Praziquantel/therapeutic use
9.
Acta Trop ; 176: 288-292, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28865900

ABSTRACT

The emergence of resistance to albendazole has encouraged the search for effective alternatives for cysticercosis and other parasitosis treatment. RCB15 is a benzimidazole derivative that may be used against such diseases. The aim of this study was to determine the in vitro effect of RCB15 on the alternative energetic pathways of Taenia crassiceps cysticerci. The cysticerci were in vitro exposed to albendazole sulphoxide (ABZSO) or RCB15 at different concentrations during 24h. The cysticerci extract and the culture medium were analyzed through spectrophotometry and high performance liquid chromatography as to detect glucose, urea, creatinine and organic acids of the energetic metabolism. The drugs did not influence the protein catabolism. Fatty acids oxidation was enhanced through significantly higher acetate concentrations in the groups treated with RCB15 and ABZSO. Beta-hydroxybutyrate concentrations were decreased which indicates the use of fatty acids towards acetyl-CoA synthesis. There was a decrease in glucose uptake and pyruvate concentrations. The absence of lactate indicates the use of pyruvate in gluconeogenesis. Therefore it is possible to conclude that RCB15 enhanced the alternative energetic pathways of cysticerci in vitro exposed to different concentration, with emphasis on the fatty acids catabolism.


Subject(s)
Anticestodal Agents/pharmacology , Benzimidazoles/pharmacology , Cysticercus/drug effects , Albendazole/analogs & derivatives , Albendazole/pharmacology , Animals , Dose-Response Relationship, Drug , Energy Metabolism/drug effects , Glucose/metabolism , Glycolysis , Lactic Acid/metabolism , Oxidation-Reduction/drug effects , Pyruvic Acid/metabolism
10.
Exp Parasitol ; 172: 12-17, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27884580

ABSTRACT

Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic benzimidazoles due to a differentiated site of action with similar outcome.


Subject(s)
Albendazole/analogs & derivatives , Anticestodal Agents/pharmacology , Benzimidazoles/pharmacology , Citric Acid Cycle/drug effects , Cysticercus/drug effects , Cysticercus/metabolism , Energy Metabolism/drug effects , Albendazole/pharmacology , Animals , Glucose/metabolism , Glycolysis/drug effects
11.
Acta Trop ; 161: 100-5, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27269203

ABSTRACT

The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100nm, while P188- and P407-based nanosuspensions had particle sizes of 74nm and 285nm, respectively. The zeta potential was -8.1, -8.6, and -13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines.


Subject(s)
Cysticercosis/drug therapy , Cysticercosis/physiopathology , Cysticercus/drug effects , Cysticercus/metabolism , Praziquantel/therapeutic use , Taenia/drug effects , Taenia/metabolism , Animals , Mice , Mice, Inbred BALB C , Nanoparticles
12.
PLoS Negl Trop Dis ; 10(2): e0004418, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26849048

ABSTRACT

BACKGROUND: Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. METHODS AND PRINCIPAL FINDINGS: PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. CONCLUSIONS: Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Albendazole/therapeutic use , Anthelmintics/therapeutic use , Cysticercus/drug effects , Granuloma/drug therapy , Adolescent , Animals , Child , Cysticercus/growth & development , Drug Therapy, Combination , Female , Granuloma/parasitology , Humans , Male , Randomized Controlled Trials as Topic , Treatment Outcome , Young Adult
13.
J Helminthol ; 90(1): 113-6, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25120032

ABSTRACT

An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of 21 (23.8%) female lambs, is reported. Gross post-mortem examinations and histology showed Cysticercus tenuicollis as the cause of death. Biochemical parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the clinical condition and biochemical parameters was observed up to 30 days following treatment.


Subject(s)
Anthelmintics/administration & dosage , Cysticercosis/veterinary , Praziquantel/administration & dosage , Sheep Diseases/drug therapy , Taenia/drug effects , Acute Disease/therapy , Animals , Cysticercosis/drug therapy , Cysticercosis/parasitology , Cysticercus/drug effects , Cysticercus/growth & development , Cysticercus/physiology , Female , Liver/parasitology , Sheep , Sheep Diseases/parasitology , Taenia/growth & development , Taenia/physiology
14.
Parasitology ; 143(4): 488-93, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26707797

ABSTRACT

Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, ß-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in ß-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.


Subject(s)
Albendazole/analogs & derivatives , Anticestodal Agents/pharmacology , Benzimidazoles/pharmacology , Cysticercus/drug effects , Energy Metabolism/drug effects , 3-Hydroxybutyric Acid/metabolism , Acetoacetates/metabolism , Albendazole/pharmacology , Animals , Creatinine/analysis , Culture Media/chemistry , Cysticercus/metabolism , Fumarates/analysis , Mice , Propionates/metabolism , Proteins/analysis , Taenia/drug effects , Taenia/metabolism , Urea/analysis
15.
Int J Parasitol ; 45(12): 749-59, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26336013

ABSTRACT

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antiparasitic Agents/administration & dosage , Brain/pathology , Cysticercosis/veterinary , Swine Diseases/drug therapy , Swine Diseases/pathology , Taenia solium/drug effects , Albendazole/administration & dosage , Animals , Brain/diagnostic imaging , Cysticercosis/drug therapy , Cysticercosis/pathology , Cysticercus/drug effects , Cysticercus/immunology , Cytokines/biosynthesis , Enzyme-Linked Immunosorbent Assay , Magnetic Resonance Imaging , Polymerase Chain Reaction , Prednisolone/administration & dosage , Radiography , Swine , Taenia solium/immunology , Treatment Outcome
16.
Exp Parasitol ; 156: 79-86, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26072200

ABSTRACT

In the search of new alternatives for neurocysticercosis treatment, the cysticidal activity of organic extracts of Teloxys graveolens was evaluated. The in vitro activity of hexane, ethyl acetate and methanol extracts against Taenia crassiceps cysts was tested and the selectivity index relative to human fibroblasts was determined. Subsequently, the in vivo efficacy of the methanolic extract at doses of 200 and 500 mg/kg in the murine cysticercosis model was evaluated. The ultrastructural effects in vitro and in vivo of the methanolic extract were also investigated using scanning electron microscopy. Additionally, a bioassay-guided fractionation for the isolation of the cysticidal components was performed. Our in vitro findings revealed that all extracts exhibited good cysticidal activity with EC50 values from 44.8 to 67.1 µg/mL. Although the ethyl acetate and methanolic extracts displayed low cytotoxicity, the methanolic extract was the most selective. The methanolic extract also showed in vivo efficacy which was similar to that obtained with ABZ. Significant alterations were found on the germinal layer of the cysts, with a high accumulation of granules of glycogen and vacuoles. The bioguided fractionation of methanolic extract led to the isolation of three flavonoids: chrysin, pinocembrin and pinostrobin; among them, pinocembrin was the compound that displayed cysticidal activity. This is the first study which reveals that T. graveolens could be a potential source for cysticidal and non-toxic compounds.


Subject(s)
Amaranthaceae/chemistry , Cysticercosis/drug therapy , Cysticercus/drug effects , Plant Extracts/pharmacology , Animals , Biological Assay , Cysticercus/ultrastructure , Female , Fibroblasts/drug effects , Flavanones/chemistry , Flavanones/isolation & purification , Flavanones/pharmacology , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Gingiva/cytology , Humans , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission , Plant Components, Aerial/chemistry , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Plant Extracts/toxicity
17.
Mol Biochem Parasitol ; 201(1): 16-25, 2015 May.
Article in English | MEDLINE | ID: mdl-26024834

ABSTRACT

Previously, we have studied the effect of the gold-compound auranofin (AF) on both thioredoxin-glutathione reductasa (TGR) activity and viability of Taenia crassiceps cysticerci. It was demonstrated that micromolar concentrations of AF were high enough to fully inhibit TGR and kill the parasites. In this work, the dynamics of changes in the glutathione pool of T. crassiceps cysticerci following the addition of AF, was analyzed. A dose-dependent decrease in the internal glutathione concentration, concomitant with an increase in ROS production was observed. These changes were simultaneous with the formation of glutathione-protein complexes and the export of glutathione disulfide (GSSG) to the culture medium. Incubation of cysticerci in the presence of both AF and N-acetyl cysteine (NAC) prevents all the above changes, maintaining cysticerci viability. By contrast, the presence of both AF and buthionine sulfoximine (BSO) resulted in a potentiation of the effects of the gold compound, jeopardizing cysticerci viability. These results suggest the lethal effect of AF on T. crassiceps cysticerci, observed at micromolar concentrations, can be explained as a consequence of major changes in the glutathione status, which results in a significant increase in the oxidative stress of the parasites.


Subject(s)
Auranofin/toxicity , Glutathione/analysis , Oxidants/toxicity , Oxidative Stress , Taenia/chemistry , Taenia/drug effects , Acetylcysteine/metabolism , Animals , Antioxidants/metabolism , Buthionine Sulfoximine/metabolism , Cysticercus/chemistry , Cysticercus/drug effects , Cysticercus/physiology , Reactive Oxygen Species/analysis , Survival Analysis , Taenia/physiology
18.
Article in Chinese | MEDLINE | ID: mdl-26930940

ABSTRACT

OBJECTIVE: To explore the clinical application value of diagnostic therapy of praziquantel for suspected cerebral cysticercosis. METHODS: The suspected cerebral cysticercosis patients were collected and treated with the diagnostic therapy [praziquantel, 50 mg/(kg · d)], and followed up for 1-2 years. RESULTS: Totally 94 suspected cerebral cysticercosis patients were collected. After the diagnostic therapy, 78 (82.98%) cases were confirmed as cerebral cysticercosis, 13 (13.83%) were diagnosed as other diseases, and 3 (3.19%) were not definitely diagnosed. CONCLUSION: The diagnostic therapy for suspected cerebral cysticercosis can reduce or avoid the missed diagnosis and misdiagnosis in some atypical cerebral cysticercosis patients.


Subject(s)
Cysticercus/drug effects , Neurocysticercosis/diagnosis , Neurocysticercosis/drug therapy , Praziquantel/therapeutic use , Adolescent , Adult , Aged , Animals , Anthelmintics/therapeutic use , Child , Child, Preschool , Cysticercus/physiology , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurocysticercosis/parasitology , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
19.
Exp Parasitol ; 149: 1-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25500213

ABSTRACT

In the search of new alternatives for neurocysticercosis treatment, Taenia crassiceps ORF strain cysticerci have been used instead of T. solium for in vitro studies. Up to date, the main criteria for the use of the murine cysticercosis model for drug efficacy evaluation have not been assessed. The aim of the present study was to evaluate the influence of two of the main variables related to the in vivo efficacy: the length of drug treatment and the starting time of treatment after experimental infection, using albendazole (ABZ) and praziquantel (PZQ) as test drugs. Additionally, the relationship between the number of cysts and the parasite weight was assessed. For the study, female BALB/c mice were experimentally infected with T. crassiceps cysts. Three different post-infection periods (10, 20 and 30 days) and three different lengths of treatment with ABZ or PZQ (10, 20 and 30 days) were selected. The efficacy of each treatment was evaluated by comparison with a control group. Our results show that for in vivo efficacy studies, the best time to start the drug treatment is 10 days post-infection and that a minimum of 20 days of treatment is required when ABZ or PZQ are used as positive control. Moreover, in this model the parasite weight can be used as a rapid tool to measure the in vivo drug activity.


Subject(s)
Albendazole/therapeutic use , Anthelmintics/therapeutic use , Cysticercosis/drug therapy , Praziquantel/therapeutic use , Albendazole/administration & dosage , Animals , Anthelmintics/administration & dosage , Cysticercosis/parasitology , Cysticercus/drug effects , Disease Models, Animal , Drug Administration Schedule , Drug Evaluation, Preclinical , Female , Mice , Mice, Inbred BALB C , Praziquantel/administration & dosage , Time Factors
20.
Exp Parasitol ; 137: 14-20, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24309372

ABSTRACT

The present study aimed to notify the history of albendazole sulphoxide (ALB-SO) and albendazole (ALBZ) efficacy against Taenia saginata cysticercus (Cysticercus bovis) parasitizing experimentally infected bovines. A total of 11 efficacy trials were performed between the years of 2002 and 2010. In order to perform these trials, animals were individually inoculated with 2×10(4) eggs of T. saginata in each study's day zero (D0). For every trial, a positive control group (untreated infected animals) and a negative control group (animals that were neither infected nor treated) were used. ALB-SO or ALB were administered in the different dosages, in different days of treatments. In a last study with this formulation, this active principle was administered orally, mixed with the mineral supplement, on the 60th DPI, in a dosage of 30mg/kg. In all trials, on the 100th DPI, all animals were euthanized and submitted to the sequenced slicing of 26 anatomical segments (fragments of approximately five millimeters) for the survey of T. saginata cysticercus. With the obtained results it is possible to verify that in the first trials, conducted in 2002, ALB-SO reached, independently of dosage and treatment scheme, efficacies superior to 98% (arithmetic means). The trials conducted in 2005 (2.5mg/kg on the 30th, 60th, and 90th DPI) obtained values of efficacy all inferior to 60%. In 2008, the trials with 2.5 and 7.7mg/kg demonstrated efficacy values inferior to 40%, for both dosages and treatment schemes (30th/60th/90th DPI and 60th DPI). When this formulation was administered orally on the dosage of 30mg/kg on the 60th DPI, the efficacy against T. saginata cysticercus reached 88.28%. ALB administered orally showed efficacy values of 0.0%, 29.88% and 28.64% in the dosages of 5, 10 and 15mg/kg, respectively, using the treatment schemes described above for each dosage. Based on the results of these trials, conducted in an eight year period (2002-2010) using the sequenced slicing method for evaluating the efficacy of the aforementioned formulations against T. saginata cysticercus, it is possible to observe that, amongst the few molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO, administered in varied routes, dosages and treatment schemes, the studies conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C. bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata larvae parasitizing experimentally infected bovines. However, future studies using molecular biology will be necessary to assess whether the difference on the efficacy of the ALB-SO can be related to strain or another specific factor.


Subject(s)
Albendazole/analogs & derivatives , Anticestodal Agents/therapeutic use , Cattle Diseases/drug therapy , Cysticercosis/veterinary , Taenia saginata/drug effects , Administration, Oral , Albendazole/administration & dosage , Albendazole/pharmacology , Albendazole/therapeutic use , Animals , Anticestodal Agents/administration & dosage , Anticestodal Agents/pharmacology , Cattle , Cattle Diseases/parasitology , Cysticercosis/drug therapy , Cysticercosis/parasitology , Cysticercus/drug effects , Dose-Response Relationship, Drug , Humans , Injections, Subcutaneous/veterinary
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