Center for the Study in Animal Science, University of Porto, (CECA/ICETA), Rua de D. Manuel II, Apt 55142, 4051-401 Porto, Portugal.
Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Biomolecules. 2019 Feb 5;9(2):54. doi: 10.3390/biom9020054.
Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving and newly transformed schistosomula (NTS) of . For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.
血吸虫病是一种主要的被忽视热带病。以有效对抗寄生虫的吡喹酮 (PZQ) 治疗血吸虫病本身并不能对抗感染相关的疾病病变，包括肝纤维化。迫切需要新的治疗方法。由于它们的生物学特性，抗氧化生物分子可能在治疗和逆转相关的病理后遗症方面有用。在这里，我们研究了一种基于驱虫药物与抗氧化生物分子联合的新治疗方法。我们使用了一种涉及 和新转化的血吸虫幼体 (NTS) 的宿主-寄生虫模型。对于体外药物筛选试验，选择了几种抗氧化剂，不仅评估了抗血吸虫活性，还评估了增强驱虫药物吡喹酮 (PZQ) 和青蒿琥酯 (AS) 活性的能力。使用倒置和自动化显微镜每天评估化合物单独/联合引起的形态改变，通过荧光法基于方法来量化 NTS 的活力。研究结果表明，不仅一些抗氧化剂提高了两种驱虫剂的抗血吸虫活性，而且它们本身就具有活性，导致 NTS 暴露后死亡率很高。PZQ + Mel (CI = 0.80)、PZQ + Resv (CI = 0.74)、AS + Resv (CI = 0.34)、AS + NAC (CI = 0.89)、VDT + Flav (CI = 1.03) 和 VDT + Resv (CI = 1.06) 的组合指数 (CI) 表明它们显示出中度至强协同作用。具有不同作用机制的化合物的组合可能为治疗血吸虫病相关疾病提供有价值的辅助作用。
