Cytochalasin D abolishes the schistosomicidal activity of praziquantel

Pica‐Mattoccia, Livia; Valle, Cristiana; Basso, Annalisa; Troiani, Anna Rita; Vigorosi, Fabio; Liberti, Piero; Festucci, Alfredo; Cioli, Donato

doi:10.1016/j.exppara.2006.09.017

Cited by 51 publications

(52 citation statements)

References 20 publications

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“…In the same study cytochalasin D, an actin depolymerizing agent, rendered the parasites completely refractory to PZQ [64], a finding that is also consistent with Ca 2þ channel involvement, since cytochalasin D is known to block the functioning of these channels in several experimental systems. In a subsequent study, however, a complete reassessment of these results was made, since it was demonstrated that cytochalasin D does not block Ca 2þ influx into schistosomes and that a large Ca 2þ uptake after PZQ exposure is perfectly compatible with parasite survival both in adult worms pretreated with cytochalasin D and in immature (drug refractory) schistosomes [65 ].…”

Section: Ca 2r Channelssupporting

confidence: 55%

“…In support of the Ca 2þ channels hypothesis it was found that two compounds which blocked their action, namely nicarpidine and nifedipine, allowed about 50% of S. mansoni worms to survive a concentration of PZQ that was normally lethal [64]. In the same study cytochalasin D, an actin depolymerizing agent, rendered the parasites completely refractory to PZQ [64], a finding that is also consistent with Ca 2þ channel involvement, since cytochalasin D is known to block the functioning of these channels in several experimental systems.…”

Section: Ca 2r Channelsmentioning

confidence: 92%

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Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

Doenhoff

Cioli²,

Utzinger³

2008

Current Opinion in Infectious Diseases

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713

566

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Section: Ca 2r Channelssupporting

confidence: 55%

Section: Ca 2r Channelsmentioning

confidence: 92%

Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

Doenhoff

Cioli²,

Utzinger³

2008

Current Opinion in Infectious Diseases

Self Cite

713

566

View full text Add to dashboard Cite

show abstract

“…Diverse studies have focused on the phenomenon (Table 3). Initially, it was hypothesized that PZQ1 affects Ca 2ϩ influx through voltage-operated calcium channels (67)(68)(69)(70)(71)(72)(73). However, in subsequent studies, it was shown that calcium accumulation by itself, as measured in parasites maintained in vitro, may not explain the schistosomicidal activity of PZQ1 (71,72).…”

Section: How Does Pzq Kill Schistosomes?mentioning

confidence: 99%

Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance

Vale

Gouveia

Rinaldi

et al. 2017

Antimicrob Agents Chemother

292

244

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Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drugresistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.

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“…However, evidence of emerging drug resistance and low efficacy of PZQ have been reported in Egypt and Senegal (1). Moreover, the possibility that PZQ binds to host actin cannot be entirely precluded (9,22,28). Accordingly, it is imperative to develop new effective drugs for treatment and prevention of the infection (4).…”

mentioning

confidence: 99%

In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium

Ridi

Aboueldahab

Tallima

et al. 2010

Antimicrob Agents Chemother

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The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy.

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Cytochalasin D abolishes the schistosomicidal activity of praziquantel

Cited by 51 publications

References 20 publications

Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis

Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance

In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium

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