一种针对血吸虫成熟不同阶段的改型药物达芙蓉的潜在抗血吸虫作用。

IF 1.8 3区 医学 Q2 PARASITOLOGY Parasitology Research Pub Date : 2024-11-30 DOI:10.1007/s00436-024-08418-4
Nahla El Skhawy, Hala E Diab, Sarah Ahmed Hassan, Aceel Y Hassan
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引用次数: 0

摘要

尽管对抗血吸虫病的实验性试验历史悠久,但由于耐药性和标准治疗仅针对成熟阶段的有效性,而忽略了其他早期发育阶段,因此它仍然是一个重大负担,从而导致严重的永久性病理后遗症。因此,重新利用一种常用的众所周知的安全药物将是一个明智的选择。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。与标准抗血吸虫药物吡喹酮相比,在感染后第0天、第21天和第42天,分别给药100 mg/kg/只小鼠,用于曼氏血吸虫侵袭期、未成熟期和成熟期。感染后第49天处死所有小鼠。与未治疗的对照组相比,DAF诱导总蠕虫和雌性蠕虫数量、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脏卵子数量显著减少。所有daf处理组肝脏丙二醛(MDA)水平均显著降低。扫描电镜结果显示,所有daf治疗组的雄性被膜均出现水肿、被膜泡、裂缝和裂隙,并伴有腹侧吸盘变形和口腔吸盘棘的紊乱。daf处理组雌虫被盖水肿,后端棘缺失。与文献记载的曼氏梭菌感染未治疗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。
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Potential anti-schistosomal effect of Daflon, a repurposed drug targeting different stages of Schistosome maturity.

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.

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来源期刊
Parasitology Research
Parasitology Research 医学-寄生虫学
CiteScore
4.10
自引率
5.00%
发文量
346
审稿时长
6 months
期刊介绍: The journal Parasitology Research covers the latest developments in parasitology across a variety of disciplines, including biology, medicine and veterinary medicine. Among many topics discussed are chemotherapy and control of parasitic disease, and the relationship of host and parasite. Other coverage includes: Protozoology, Helminthology, Entomology; Morphology (incl. Pathomorphology, Ultrastructure); Biochemistry, Physiology including Pathophysiology; Parasite-Host-Relationships including Immunology and Host Specificity; life history, ecology and epidemiology; and Diagnosis, Chemotherapy and Control of Parasitic Diseases.
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