Zoology Department, Faculty of Science, Damietta University, New Damietta 34517, Egypt.
Zoology Department, Faculty of Science, Damietta University, New Damietta 34517, Egypt.
Biomed Pharmacother. 2018 Mar;99:570-575. doi: 10.1016/j.biopha.2018.01.098. Epub 2018 Feb 20.
Increasing resistance to praziquantel, the only available antischistosomal drug, is always developed by schistosomes. The recent description of stem cell-like neoblasts in schistosomes led to the idea of applying antineoplastic drugs as antischistosomal agents that may inhibit stem cell divisions and retard worm regeneration. Here, we explored the in vitro and in vivo effect of some antineoplastic drugs on S. mansoni worm and the host mouse liver. S. mansoni worms' viability was tested after exposure to either praziquantel or one of the antitumor drugs (hydroxyurea, cisplatin, methotrexate, and colchicine) in vitro for 24 and 48 h. The effect of two of them (hydroxyurea and cisplatin) on worm burden, tegument ultrastructure, and host liver structure and function was tested in vivo in S. mansoni-infected mouse model. All drugs affected variably the worm burden in vitro. Hydroxyurea and cisplatin, like praziquantel, damaged the worm tegument, reduced worm burden, and viable schistosome eggs, decreased anti-schistosome IgG, reduced egg-induced hepatic granuloma size and cellularity, restored liver organization and improved liver function as represented by serum alanine aminotransferase and albumin. In conclusions, a single dose of hydroxyurea and cisplatin had anti-schistosome effects and may offer a safe promising alternative to control of schistosomiasis. A direct link between antitumor drugs and inhibition of schistosome neoblasts remains to be proven.
日本血吸虫对唯一可用的抗血吸虫药物吡喹酮的耐药性不断增加。最近在日本血吸虫中描述了干细胞样成体干细胞,这使得人们想到应用抗肿瘤药物作为抗血吸虫药物,这些药物可能抑制干细胞分裂并延缓蠕虫再生。在这里,我们研究了一些抗肿瘤药物对曼氏血吸虫成虫及其宿主小鼠肝脏的体外和体内作用。在体外分别用吡喹酮或其中一种抗肿瘤药物(羟基脲、顺铂、甲氨蝶呤和秋水仙碱)处理 24 和 48 小时后,检测曼氏血吸虫成虫的活力。在曼氏血吸虫感染的小鼠模型中,体内研究了其中两种药物(羟基脲和顺铂)对虫荷、表皮超微结构以及宿主肝脏结构和功能的影响。所有药物均不同程度地影响体外的虫荷。羟基脲和顺铂与吡喹酮一样,损伤虫体表皮,降低虫荷和有活力的血吸虫卵,降低抗血吸虫 IgG,降低卵诱导的肝肉芽肿大小和细胞数,恢复肝脏组织并改善肝功能,表现为血清丙氨酸氨基转移酶和白蛋白。总之,羟基脲和顺铂的单剂量具有抗血吸虫作用,可能为控制血吸虫病提供一种安全有前景的替代方法。抗肿瘤药物与抑制血吸虫成体干细胞之间的直接联系仍有待证明。