Determination of ED50 values for praziquantel in praziquantel-resistant and -susceptible Schistosoma mansoni isolates

Cioli, Donato; Botros, Sanaa S.; Wheatcroft-Francklow, Katherine; Mbaye, Amadou; Southgate, V. R.; Tchuenté, Louis-Albert Tchuem; Pica‐Mattoccia, Livia; Troiani, Anna Rita; el-Din, Sayed H. Seif; Sabra, Abdel-Nasser A.; Albin, Jan; Engels, Dirk; Doenhoff, Michael J.

doi:10.1016/j.ijpara.2004.05.001

Cited by 117 publications

(74 citation statements)

References 33 publications

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“…We have identified a thioredoxin gene encoding a mitochondrial protein and have evidence that the S. mansoni thioredoxin-glutathione reductase mRNA is alternatively spliced to produce a mitochondrial form of the protein. 4 Therefore, the mitochondria of schistosomes have a complete thioredoxin-based redox regulatory system.…”

Section: Discussionmentioning

confidence: 99%

“…In the coming years the Schistosomiasis Control Initiative and endemic country programs will treat hundreds of millions of people with praziquantel, the single anti-schistosomiasis drug in widespread use (3). There is already clinical and laboratory evidence for the existence of praziquantel resistance parasites (4), and widespread use is expected to generate strong selective pressure for drug resistance. Clearly there is an urgent need for new anti-schistosome drugs.…”

mentioning

confidence: 99%

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Redox Balance Mechanisms in Schistosoma mansoni Rely on Peroxiredoxins and Albumin and Implicate Peroxiredoxins as Novel Drug Targets

Sayed

Cook

Williams

2006

Journal of Biological Chemistry

110

108

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Redox Balance Mechanisms in Schistosoma mansoni Rely on Peroxiredoxins and Albumin and Implicate Peroxiredoxins as Novel Drug Targets

Sayed

Cook

Williams

2006

Journal of Biological Chemistry

110

108

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“…The drug was dispersed in water with 2% Cremophor-EL (Sigma-Aldrich, St. Louis, MO, USA), a fresh batch of doses was prepared, and it was administered by oral gavage to each mouse according to each animal's body weight. Two weeks after the end of treatment (9 weeks postinfection), animals were sacrificed and perfused, and the worm burden was quantified (16) for estimation of percent worm reduction and assessment of PZQ 50% effective dose (ED 50 ) (17). After perfusion, a piece of liver and one of intestine were taken to count the number of eggs per gram of these tissues (18), while another piece of the small intestine was used to determine the percentage of the different egg developmental stages (19).…”

Section: Methodsmentioning

confidence: 99%

Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

El-Feky

Mohamed

Nasr

et al. 2015

Antimicrob Agents Chemother

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c Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61-and 1.96-fold and 2.16-and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC 0 -8 ) and maximum concentration of drug in serum (C max ), with a decrease in elimination rate constant (k el ) by 2.84-and 1.35-fold and increases in the absorption rate constant (k a ) and half-life (t 1/2e ) by 2.11-and 1.51-fold and 2.86-and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED 50 ] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ. Schistosomiasis is a parasitic disease caused by blood flukes of the genus Schistosoma and is a serious public health problem in almost 70 countries of the tropics and subtropics without potable water and with poor sanitary conditions. It is estimated that at least 230 million people need treatment against schistosomiasis per year (1). Since an effective vaccine against schistosomiasis is lacking, the emphasis today is placed on the drug praziquantel (PZQ) (2). The low cost has made presumptive treatment on the basis of early clinical symptoms, or even universal treatment, costeffective in many situations (3).Although PZQ has proved to be especially useful in the treatment of schistosomiasis, it sometimes fails to give complete cures in treated populations. The failure of mass treatment to control schistosomiasis has been attributed to the fact that therapy is not sufficiently long-lasting (4). This effect can occur because of the low bioavailability of praziquantel d...

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“…However, there is concern that tolerance or resistance to praziquantel may be developing [57][58][59]. The possibility of selecting schistosomes largely insensitive to praziquantel has been demonstrated experimentally in mice after administration of several sub-curative doses [60].…”

Section: Drug Resistance To Praziquantel and Artemethermentioning

confidence: 99%

Discovering New Schistosome Drug Targets: The Role of Transcriptomics

Gobert¹,

Jones²

2008

CDT

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Microarrays are a platform resource that allow the analysis of the entire transcriptome profile of an organism. New advances in the design and production phases make microarrays the perfect tool for parasitology. The mode of action of many drugs employed to treat parasitic diseases are not understood and coupled with rising concerns of drug resistance, all emphasises the importance of research into the interactions drugs have on their target transcriptomes. One particular disease schistosomiasis, relies on a limited number of chemotherapies for treatment and is a prime example of the need for detailed gene expression information while under drug pressure. Recent microarray studies investigating the basic biology of the major species of Schistosoma and their associated microarray platforms, have provided the basis for future drug mode of action/ drug resistance studies. However determining what is a direct gene expression change due to drug treatment is a hurdle that must be addressed both at the level of parasitology and general toxicology. The utilisation of time-course and/or drug concentration studies, and generic stress inducers, in combination with advanced statistical/bioinformatical methods will allow the separation of direct, indirect and generic gene expression responses. It is hoped that with these approaches the future investigation of complex biological and physiological questions such as drug mode of action or drug resistance in parasitology may be addressed.

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Determination of ED50 values for praziquantel in praziquantel-resistant and -susceptible Schistosoma mansoni isolates

Cited by 117 publications

References 33 publications

Redox Balance Mechanisms in Schistosoma mansoni Rely on Peroxiredoxins and Albumin and Implicate Peroxiredoxins as Novel Drug Targets

Redox Balance Mechanisms in Schistosoma mansoni Rely on Peroxiredoxins and Albumin and Implicate Peroxiredoxins as Novel Drug Targets

Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

Discovering New Schistosome Drug Targets: The Role of Transcriptomics

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