Fasciola hepatica: time-dependent disruption of spermatogenesis following in vivo treatment with triclabendazole

Abstract

Sheep infected with the Cullompton isolate of Fasciola hepatica were treated with triclabendazole at a concentration of 10 mg/kg at 12 weeks post-infection. Adult flukes were recovered from the liver and, where present, from the gall bladder at 48, 72 and 96 h post-treatment (pt). Gross changes to the spermatogenic cells of the testis were examined by histology and ultrastructural alterations were visualised via transmission electron microscopy. Disruption was progressive in nature, with the testis tubules becoming shrunken, vacuolated and gradually more denuded of cellular content over the 96-h time period. From 48 h pt, the number of primary and secondary spermatogonia decreased and multinucleate spermatogonial cells were frequent. Later, developmental stages were uncommon, giving rise to much empty space within the tubules. By 72 h pt, the tubules contained many apoptotic and degraded cells and had an extremely disorganised appearance. At 96 h pt, the tubules were almost completely empty, with the exception of the remains of degraded spermatogenic cells. These results indicate that triclabendazole severely disrupts spermatogenesis in the liver fluke from 48 h pt in vivo.

Microscopic alterations in Fasciola hepatica from sheep treated with albendazole

“…The morphological characteristics observed for the control animal are consistent with those observed by Hanna et al (2008Hanna et al ( , 2010, McConville et al (2010), and Toner et al (2011) for F. hepatica specimens not exposed to anthelmintic. Spermatogonia and primary spermatocytes were observed to occupy the entire region of the testis tubule, thereby ensuring the production of viable sperm and, consequently, F. hepatica eggs.…”

“…Two F. hepatica specimens from each animal were selected from and placed between slides and were fixed in Bouin solution for 24 hours. After this period, the specimens were histologically processed following the methodology of Toner et al (2011) with modifications, in which the specimens remained for 15 minutes in ethanol at 70 °G.L. Next, each specimen was cross-sectioned in the region that corresponded to the location of the reproductive system, which encompasses the right and left halves and the median plane.…”

“…Several studies have histologically evaluated F. hepatica samples obtained from sheep treated with triclabendazole (HANNA et al, 2010(HANNA et al, , 2012TONER et al, 2011). However, no studies were found in the literature addressing F. hepatica obtained from sheep treated with albendazole.…”

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

“…The loss of motility and the degeneration of the gastrodermal cells (seen by 72 h pt) (Toner et al, 2010b) would prevent the fluke from feeding and this would exacerbate the general disruption of the fluke. Changes to the reproductive system took place earlier: for example, the testis was severely affected by 48 h pt (Toner et al, 2011b) and no eggs were present in the uterus at this time (Toner et al, 2011a). The latter was due to the disruption of the ovary, vitelline follicles and Mehlis' gland, which provide the components for egg formation in the ootype (Toner et al, 2011a).…”

“…One group of drugs derived from natural sources that has received much attention in recent years is the artemisinins. Semi-and fully-synthetic derivatives of the artemisinins are the mainstay of malaria treatment programmes and have been used against schistosomes (e.g., Woodrow et al, 2005;Utzinger et al, 2007). Several studies have demonstrated their activity against adult and juvenile F. hepatica under in vitro conditions and in the rodent (rat) model (results reviewed by Fairweather, 2009).…”