Leitch B, Probert A J
Exp Parasitol. 1984 Dec;58(3):278-89. doi: 10.1016/0014-4894(84)90045-6.
Amoscanate, when administered orally as an aqueous or "formulated" preparation, induced pronounced ultrastructural abnormalities in male and female Schistosoma haematobium. Higher dose levels of the aqueous suspension (300 mg/kg body wt) had to be administered to achieve the full range of effects induced by formulated doses of 2.5-8 mg/kg body wt. Worms were recovered from hamsters between 1 and 120 hr after treatment. Although the amount of amoscanate-induced damage varied considerably between worms, an overall pattern of damage emerged. Initially, 1 hr after treatment, amoscanate caused tegumental vacuolation and oedema. As the drug treatment period was extended to 24 hr, blebbing, exudation, collapse of sensory organelle bases, and abnormal mitochondria became increasingly evident. With exposure to higher drug doses (50-300 mg/kg body wt), the tegument became further distorted with the appearance of necrotic structures and myelin whorls, which appeared to represent various stages in lysosomal formation and digestion. Eventually, erosion of surface layers resulted in the breakdown of tegumental integrity. The caeca and vitellaria were also adversely affected by drug treatment. Basal vacuolation and the formation of myelin whorls occurred in the gastrodermis. In the mature S4 vitelline cells, coalesced vitelline droplets and myelin whorls were evident.
当以水性或“配制好的”制剂口服给药时，硝硫氰胺能在埃及血吸虫雌雄虫体中引起明显的超微结构异常。必须给予更高剂量水平的水悬液（300毫克/千克体重）才能达到2.5至8毫克/千克体重的配制剂量所诱导的全部效应。在治疗后1至120小时从仓鼠体内回收虫体。虽然硝硫氰胺引起的损伤量在不同虫体之间有很大差异，但总体损伤模式显现出来。最初，治疗后1小时，硝硫氰胺引起皮层空泡化和水肿。随着药物治疗时间延长至24小时，起泡、渗出、感觉细胞器基部塌陷以及线粒体异常变得越来越明显。暴露于更高药物剂量（50至300毫克/千克体重）时，皮层进一步扭曲，出现坏死结构和髓鞘样小体，这似乎代表了溶酶体形成和消化的不同阶段。最终，表层侵蚀导致皮层完整性破坏。盲肠和卵黄腺也受到药物治疗的不利影响。胃皮层出现基部空泡化和髓鞘样小体形成。在成熟的S4卵黄细胞中，卵黄滴融合和髓鞘样小体明显可见。
