Kamel Reem Osama A, Bayaumy Fatma El-Zahraa Anwar
Ain Shams University, Women College for Arts, Science and Education, Department of Zoology, Asmaa Fahmey St., Cairo, Egypt.
Mem Inst Oswaldo Cruz. 2017 Apr;112(4):247-254. doi: 10.1590/0074-02760160324. Epub 2017 Mar 2.
Praziquantel has been cited as the only drug for treating schistosomiasis. However, concerns over drug resistance have encouraged the search for novel drug leads. The antimalarial drug primaquine possesses interesting anti-schistosmal properties.
This study is the first to document the potential role of primaquine as a schistosomicide and the ultrastructural changes induced by primaquine on juvenile or adult male worms of Schistosoma mansoni.
Ultrastructural alterations in the tegumental surface of 21-day-old juvenile and adult male worms of S. mansoni were demonstrated following primaquine treatment at different concentrations (2, 5, 10, 15, and 20 µg/mL) and incubation periods (1, 3, 6, 24, and 48 h) in vitro, using both scanning and transmission electron microscopy.
At low concentrations (2, 5, and 10 µg/mL) both juvenile and adult male worms were alive after 24 h of incubation, whereas contraction, paralysis, and death of all worms were observed after 24 h of drug exposure at 20 µg/mL. The tegument of juvenile and adult male worms treated with primaquine exhibited erosion, peeling, and sloughing. Furthermore, extensive damage of both tegumental and subtegumental layers included embedded spines, and shrinkage of muscles with vacuoles. The in vitro results confirmed that primaquine has dose-dependent effects with 20 µg/mL as the most effective concentration in a short incubation period.
The schistosomicidal activity of primaquine indicates that this drug possesses moderate in vitro activity against juvenile and adult male worms, since it caused high mortality and tegumental alterations. This study confirmed that the antimalarial drug primaquine possesses anti-schistosomal activity. Further investigation is needed to elucidate its mechanism of action.
吡喹酮一直被认为是治疗血吸虫病的唯一药物。然而,对耐药性的担忧促使人们寻找新的药物线索。抗疟药物伯氨喹具有有趣的抗血吸虫特性。
本研究首次记录了伯氨喹作为杀血吸虫剂的潜在作用以及伯氨喹对曼氏血吸虫幼虫或成年雄虫诱导的超微结构变化。
使用扫描电子显微镜和透射电子显微镜,在体外对21日龄的曼氏血吸虫幼虫和成年雄虫进行不同浓度(2、5、10、15和20μg/mL)和孵育时间(1、3、6、24和48小时)的伯氨喹处理后,观察其体表超微结构的改变。
在低浓度(2、5和10μg/mL)下,幼虫和成年雄虫在孵育24小时后仍存活,而在20μg/mL药物暴露24小时后,观察到所有虫体收缩、麻痹和死亡。用伯氨喹处理的幼虫和成年雄虫的体表出现侵蚀、剥落和脱落。此外,体表和皮下层均有广泛损伤,包括棘突嵌入、肌肉收缩和空泡形成。体外实验结果证实,伯氨喹具有剂量依赖性效应,20μg/mL是短时间孵育中最有效的浓度。
伯氨喹的杀血吸虫活性表明,该药物对幼虫和成年雄虫具有中等程度的体外活性,因为它导致了高死亡率和体表改变。本研究证实抗疟药物伯氨喹具有抗血吸虫活性。需要进一步研究以阐明其作用机制。