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Rats infected with the triclabendazole (TCBZ)-resistant Sligo isolate were dosed orally with artemether at a concentration of 200\u00a0mg\/kg and flukes recovered at 24, 48 and 72\u00a0h post treatment (pt). Rats infected with the TCBZ-resistant Oberon isolate were dosed orally with artesunate at a concentration of 200\u00a0mg\/kg and flukes recovered 24, 48, 72 and 96 h pt. The flukes were processed for histological and transmission electron microscope (TEM) examination. Changes to the spermatogenic cells were evident at 24\u00a0h pt with artemether. The spermatogonial and spermatocyte cells contained abnormal mitochondria, there were fewer spermatids and spermatozoa in the tubules than normal, and a number of cells showed signs of apoptosis. There was a further decline in cell numbers at 48\u00a0h pt and the organization of the spermatocyte and spermatid rosettes was atypical. Sperm formation had become abnormal and those spermatozoa present possessed only a single axoneme. By 72\u00a0h pt, the testis tubules were vacuolated and filled with abnormal cells and cell debris. Only spermatogonial cells could be identified and there was widespread evidence of apoptosis in the cells. Distinct cellular changes following artesunate treatment did not become apparent until 48\u00a0h pt. The changes seen were similar to those described for artemether, but were generally less severe at matching time-periods. The fine structural changes occurring in the spermatogenic cells were compared to those observed in other cell types and fluke tissues and the overall information was collated to identify the cellular targets for artemisinin action and to establish the time-line for drug action.<\/jats:p>","DOI":"10.1017\/s0022149x16000079","type":"journal-article","created":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T11:36:05Z","timestamp":1458128165000},"page":"55-71","source":"Crossref","is-referenced-by-count":10,"title":["Disruption of spermatogenesis in the liver fluke, <i>Fasciola hepatica<\/i> by two artemisinin derivatives, artemether and 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