High-performance liquid chromatographic assay for a new fasciolicide agent, αBIOF10, in biological fluids

Rivero, Lauro Misael del; Jung, Helgi; Castillo, Rafael; Hernández‐Campos, Alicia

doi:10.1016/s0378-4347(98)00145-5

Cited by 10 publications

(6 citation statements)

References 6 publications

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“…Thus, despite the strong plasma protein binding shown by TCBZ, experiments have shown that entry of this compound is predominantly across the tegument (Mottier et al 2006; Toner et al 2009). For compound alpha, it is most likely the sulphoxide and sulphone metabolites that penetrate the tegument, as they are present in the blood plasma of sheep, whereas compound alpha itself has not been detected (Rivero et al 1998; Ramírez et al 2008). In contrast to the results with compound alpha and TCBZ, disruption of the gastrodermal cells following treatment with the fasciolicides nitroxynil and clorsulon was consistently more severe than that of the tegument, pointing to oral uptake as the most important route of entry (McKinstry et al 2007; Meaney et al 2005 a , b , 2007).…”

Section: Discussionmentioning

confidence: 99%

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Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

McConville¹,

Brennan²,

Flanagan

et al. 2009

Parasitology

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Sheep infected with the triclabendazole-susceptible, Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48 and 72 h post-treatment (p.t.). Ultrastructural changes to the flukes were assessed using transmission electron microscopy (TEM), with a view to gathering information on the mechanism(s) of action for compound alpha and on the possible route of its entry into F. hepatica. The tegumental syncytium was more severely affected than the gut at all time-points p.t. with compound alpha, suggesting a predominantly trans-tegumental route of uptake. Disruption to the tegumental system became increasingly severe over time. A stress response was observed at 24 h p.t. and took the form of blebbing and increases in the production and transport of secretory bodies. By 72 h p.t., extensive tegumental loss and degeneration of the tegumental cell bodies had occurred. Degeneration of subtegumental tissues and internal flooding were also observed. Changes in the gastrodermal cells were slow to develop: reduced secretory activity was evident at 72 h p.t.. There was progressive disruption to the somatic muscle layers, with disorganization of the muscle blocks and loss of muscle fibres.

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Section: Discussionmentioning

confidence: 99%

“…While peak blood levels occur fairly quickly (10 h p.t. : Rivero et al 1998 ;Ramírez et al 2009), morphological changes take considerably longer to become apparent. They are not marked until 48 h p.t., becoming very severe by 72 h. This observation resembles the time-sequence observed with juvenile flukes (McConville et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

McConville¹,

Brennan²,

Flanagan

et al. 2009

Parasitology

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“…Alpha.SO was initially prepared as a stock solution in dimethyl sulphoxide (Me 2 SO) and added to the culture medium to give a maximum solvent concentration of 0.1% (v/v). The concentration of alpha.SO used in this study was selected so as to be comparable to maximum blood levels attained in sheep following an oral dose of 12 mg/kg compound alpha: 8.3 μg/ml at 10 h (Rivero et al 1998). Controls were prepared by incubating whole flukes in NCTC 135 medium in the absence of alpha.SO, but containing Me 2 SO.…”

Section: Methodsmentioning

confidence: 99%

Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

et al. 2006

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Juvenile triclabendazole-resistant liver flukes, Fasciola hepatica, were incubated in vitro with 10 microg/ml of the sulphoxide metabolite of the experimental fasciolicide, compound alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole], for 6 and 18 h. Following treatment, the specimens were examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry. The SEM results revealed a posterior-directed disruption comprised predominantly of swelling and blebbing of the tegument; these changes were more severe and extensive after the longer 18-h incubation. Along with swelling of the tegument and blebbing, the TEM results also revealed swelling of the mitochondria and basal infolds. A decrease in the number of both T1 and T2 secretory bodies was observed in the syncytium and cytoplasmic connections after the 18-h treatment. The circular muscle bundles were also disrupted, in that the organisation of the muscle fibres was irregular and the total number of muscle fibres was reduced. The immunocytochemical studies revealed no significant disruption to the distribution of tubulin immunoreactivity within the tegumental syncytium, the cytoplasmic connections or the associated tegumental cells. The results indicate that alpha.SO is capable of disrupting the tegument of 4-week-old triclabendazole-resistant liver flukes, though the morphological changes were not associated with any significant differences in tubulin immunostaining.

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“…The most significant changes occurred between 48 and 72 h p.t., indicating a slow action, even though maximum blood levels are reached quite quickly – after only 10–14 h p.t. (Rivero et al , 1998; Ramírez et al , 2009). The effect was more rapid with juvenile than adult flukes: after 72 h treatment, almost 90% of juvenile flukes were dead, whereas only 23% of adult flukes were dead at this time.…”

Section: Dealing With Resistancementioning

confidence: 99%

Triclabendazole progress report, 2005–2009: an advancement of learning?

Fairweather

2009

J. Helminthol.

143

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Triclabendazole (TCBZ) remains the drug of choice for treating infections of the liver fluke, Fasciola hepatica in livestock and has become the main drug used to treat human cases of the disease as well. Cases of resistance in livestock continue to be reported, suggesting that the problem is increasing. In order to address the problem, there is a need for better understanding of drug action. A 'state-of-play' review on different aspects of TCBZ activity was published by the present author in 2005. The main purpose of the current review is to assess what progress has been made in the past four years towards understanding the main aspects of drug activity, including drug pharmacokinetics and pharmacodynamics and an understanding of the mechanism(s) of resistance. Also, what advances have been made in identifying alternative compounds and using drug combinations to enhance TCBZ activity. Stemming from a number of in vivo studies, it has become evident that fluke isolates of differing sensitivity to TCBZ differ in some of their biological parameters, and information on this interesting phenomenon will be presented. An update on the use of TCBZ for human fascioliasis is also given. The review will indicate what progress has been made, but will also highlight areas that remain inadequately understood and require greater research focus.

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High-performance liquid chromatographic assay for a new fasciolicide agent, αBIOF10, in biological fluids

Cited by 10 publications

References 6 publications

Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

Triclabendazole progress report, 2005–2009: an advancement of learning?

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