Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Parasitol Res. 2024 Nov 30;123(12):402. doi: 10.1007/s00436-024-08418-4.
Despite the long history of experimental trials to combat schistosomiasis, it remains a significant burden due to drug resistance and the effectiveness of the standard treatment only against the mature stage, while skipping other early developmental stages thus leading to severe permanent pathological sequelae. Therefore, repurposing a commonly used well-known safe drug would be a wise alternative. We investigated the potential anti-schistosomal drug activity of Daflon® (DAF) against different schistosomal developmental stages. DAF was administrated at a dose of 100 mg/kg/mouse on days zero, 21, and 42 post-infection towards the invasive, immature, and mature stages of Schistosoma mansoni respectively in comparison to the standard anti-schistosomal drug (Praziquantel). All mice were sacrificed on day 49 post-infection. DAF induced a significant reduction in the total and female worm count, hepatic granuloma size, and number, the extent of liver parenchymal injury and fibrosis as well as intestinal and hepatic egg count compared to the infected untreated control. Liver malondialdehyde (MDA) levels significantly decreased in all DAF-treated groups. Scanning electron microscope findings revealed edema, tegumental blebs, cracks, and fissures in male tegument in all DAF-treated groups with distortion of the ventral suckers and disarrangement of the spines of the oral sucker. The female worm from DAF-treated groups showed tegumental edema with loss of the spines at the posterior end. Compared to the documented reduction of testosterone levels and distortion of testicular architecture in the S. mansoni-infected untreated group, DAF significantly restored testosterone levels and testicular architecture.
尽管在防治血吸虫病方面已经进行了长期的实验性研究，但由于药物耐药性以及标准治疗方法仅对成熟阶段有效，而跳过其他早期发育阶段，从而导致严重的永久性病理后遗症，血吸虫病仍然是一个重大负担。因此，重新利用一种常用的知名安全药物将是明智的选择。我们研究了 Daflon®（DAF）对不同血吸虫发育阶段的潜在抗血吸虫药物活性。DAF 以 100mg/kg/只的剂量在感染后第 0、21 和 42 天分别给予感染曼氏血吸虫的侵袭性、未成熟和成熟阶段的小鼠，与标准抗血吸虫药物（吡喹酮）进行比较。所有小鼠均在感染后第 49 天处死。与未感染未经处理的对照组相比，DAF 显著减少了总虫和雌虫计数、肝肉芽肿大小和数量、肝实质损伤和纤维化程度以及肠道和肝内虫卵计数。与未感染未经处理的对照组相比，DAF 治疗组的肝丙二醛（MDA）水平显著降低。扫描电子显微镜观察结果显示，所有 DAF 治疗组的雄虫表皮均出现水肿、表皮疱、裂缝和裂痕，腹吸盘变形，口吸盘棘刺排列紊乱。DAF 治疗组的雌虫表皮水肿，后端棘刺缺失。与未感染未经处理的 S. mansoni 感染组睾酮水平降低和睾丸结构扭曲相比，DAF 显著恢复了睾酮水平和睾丸结构。
