Electron microscopical study to assess thein vitroeffects of the synthetic trioxolane OZ78 against the liver fluke,Fasciola hepatica

Abstract

Adult Fasciola hepatica were incubated for 48 h in vitro in the synthetic peroxide, OZ78 at a concentration of 100 mg/ml and then prepared for scanning and transmission electron microscopy. There was limited disruption to the external fluke surface, with only slight swelling and blebbing of the interspinal tegument in the midbody and ventral tail regions. By contrast, significant disruption was observed to the ultrastructure of the tegument and subtegumental tissues. There was severe swelling of the basal infolds in the tegumental syncytium and the flooding spread internally to affect the subtegumental tissues. In the tegumental system, there was swelling of the cisternae of granular endoplasmic reticulum and of the mitochondria, with the latter showing signs of breaking down. Autophagic vacuoles and lipid droplets were present and the synthesis of tegumental secretory bodies was much reduced. The gastrodermal cells were severely affected, with swelling and degeneration of the mitochondria and the presence of autophagic vacuoles and lipid droplets. The granular endoplasmic reticulum was swollen and vesiculated and the cells contained few secretory bodies. Both the vitelline and testis follicles showed evidence of extensive cellular disruption and degeneration. This study confirms previous data indicating the potential flukicidal activity of OZ78.

Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica

“…The general swelling of the basal infolds, mucopolysaccharide masses, mitochondria and cisternae of GER is indicative of disruption of the osmoregulatory function of the tegument (Fairweather et al 1999). Similar observations have been made in previous studies involving TCBZ.SO (Stitt and Fairweather 1994;Halferty et al 2009a) and various other fasciolicides (Fairweather et al 1986;Skuce et al 1987;Skuce and Fairweather 1990;Anderson and Fairweather 1995;Meaney et al 2004Meaney et al , 2005Meaney et al , 2007McConville et al 2006McConville et al , 2007McConville et al , 2008McConville et al , 2009bMcKinstry et al 2007McKinstry et al , 2009Halferty et al 2009b). …”

Erratum to: Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica

“…This is indicative of disruption to the osmoregulatory function of the tegument (Fairweather et al 1999). Similar observations have been made in previous studies involving TCBZ.SO (Stitt and Fairweather 1994;Halferty et al 2009a) and various other fasciolicides (Fairweather et al 1986;Skuce et al 1987;Skuce and Fairweather 1990;Anderson and Fairweather 1995;Meaney et al 2004Meaney et al , 2005Meaney et al , 2007McConville et al 2006McConville et al , 2007McConville et al , 2008McConville et al , 2009McKinstry et al 2007McKinstry et al , 2009Halferty et al 2009b). The severe swelling of the basal infolds would account for the general swelling of the tegument observed in the previous SEM study (Devine et al 2010c); if allowed to continue, this would lead to the sloughing of the tegument.…”

A comparative study on the impact of two artemisinin derivatives, artemether and artesunate, on the female reproductive system of Fasciola hepatica

“…Nevertheless, it is important for the future design and testing of new artemisinin derivatives that there is a better understanding of their action against fluke. There have been few morphological studies and they have concentrated on external surface changes to flukes following treatment (Keiser and Morson, 2008a,b;Halferty et al, 2009;O'Neill et al, 2009O'Neill et al, , 2015Kirchhofer et al, 2011;Duthaler et al, 2012).…”

“…The main focus of the paper will be on the vitelline cells, which provide shell protein and energy reserves for egg formation. They have a very high level of secretory activity and rapid turnover, are very sensitive to drug action and previously have been good models for studies on drug action against F. hepatica Skuce and Fairweather, 1990;Stitt and Fairweather, 1996;Colhoun et al, 1998;Halferty et al, 2009;Toner et al, 2011;McConville et al, 2012). Additional histological observations on changes induced by artemether in other female tissues will provide a more complete picture of drug action and the downstream impact on egg production.…”