Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

Abstract

The ultrastructural changes in Fasciola hepatica induced by the fasciolicide clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepaticawere dosed orally with clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with clorsulon for 24 h at a concentration of 10 microg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

Effects of Mirazid® and myrrh volatile oil on adult Fasciola gigantica under laboratory conditions

“…These changes consisted of swelling, blebbing, which was later disrupted, leading to erosion and desquamation of the tegument, resulting in the lesion, and finally the exposure and disruption of basal lamina and the dislodging of spines. Swelling and blebbing were characteristic of a stress response by the fluke; they had been seen in the present study with TCBZ-SO and in previous studies with other drugs (clorsulon, albendazole, closantel, nitroxynil, compound alpha, and artemether) [9,10,[21][22][23][24]. Also, they were similar to changes on the surface of, a closely related trematode, Schistosoma mansoni treated with Mirazid襅 oleoresin [25] .…”

Effect of niclosamide on the tegumental surface of Haplorchis taichui using scanning electron microscopy

“…Similar observations were made for other anthelmintic drugs (Lee et al, 1987;Stitt & Fairweather, 1993;Apinhasmit & Sobhon, 1996;Meaney et al, 2002Meaney et al, , 2003Buchanan et al, 2003). Blebbing and swelling are early changes leading to loss of the tegument.…”

Adult triclabendazole-resistantFasciola hepatica: morphological changes in the tegument and gut followingin vivotreatment with artemether in the rat model

“…The apparent contradiction between drug peaks, drug half-life and drug action has been seen in other drug studies on F. hepatica (e.g. Meaney et al, 2003;McConville et al, 2008McConville et al, , 2009b. For these drugs, which are relatively slow-acting, it may take some time before their action (and the morphological changes they induce) to become apparent; however, the effects are seemingly irreversible, as the drug continues to act following its elimination from the host.…”

“…closantel (Skuce & Fairweather, 1990), clorsulon (Meaney et al, 2003), nitroxynil (McKinstry et al, 2003, TCBZ (Halferty et al, 2008) and the TCBZ derivative, compound alpha . The lack of serious disruption to the surface morphology of the fluke was reflected in the limited internal changes to the tegumental system observed by transmission electron microscopy.…”