Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco. Avenida Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901, Recife, PE, Brazil.
Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco. Avenida Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901, Recife, PE, Brazil.
Acta Trop. 2020 Jan;201:105159. doi: 10.1016/j.actatropica.2019.105159. Epub 2019 Sep 3.
Currently, the control of schistosomiasis is based on a single drug, praziquantel, which is effective against all species of Schistosoma but only in the adult stage, presenting a schistosomicidal deficit at the other developmental stages of the parasites. Recently our research group has demonstrated that the potassium salt of usnic acid (PS-UA) presented schistosomicidal property against couples of adult worms of S. mansoni. Thus, the present study seeks to report for the first time the in vitro activity of PS-UA against different developmental stages of S. mansoni (schistosomules and young worms). As schistosomicide parameters, we evaluated motility, mortality, cell viability of the worms and tegument changes by scanning electron microscopy (SEM). After 3 h exposure, PS-UA was lethal to schistosomules at concentrations of 100 and 50 μM, whereas for concentrations 25 and 12.5 μM, 38 and 18% of mortality and 62 and 24% changes in motility, respectively, were reached. Yet for schistosomules, concentration of 25 μM caused 90 and 100% of death after 6 and 12 h, respectively. In the concentration of 12.5 μM at intervals of 12 and 24 h mortality was 68 and 100%, respectively. For young worms, after 3 h of exposure at concentrations of 200 and 100 μM caused 57 and 27% mortality, respectively. After 12 and 24 h, these concentrations caused mortality of 90 and 100% and 47 and 60% respectively. After 24 h, concentrations of 50 and 25 μM caused 80 and 30% change in motility, respectively. However, at the 12.5 μM concentration no change was observed. In addition, PS-UA reduced the cellular viability of young worms by 50.98% and 85.87% at concentrations of 100 and 200 μM, respectively. In both stages of worms and at different exposure intervals, PS-UA caused alterations such as: dorsoventral contraction, peeling, swelling, blisters, erosion, exposure of subtegumental tissue and disintegration of tegument. According to the results, changes in motility and mortality caused by PS-UA against schistosomules and young worms were concentration and time-dependents, also PS-UA even at low concentration, was able to cause profound ultrastructural changes in the integument of the worms. PS-UA is a promising candidate as prophylactic agent in the control of schistosomiasis mansoni.
目前，血吸虫病的控制基于一种单一的药物，即吡喹酮，它对所有血吸虫物种都有效，但只在成虫阶段有效，对寄生虫的其他发育阶段表现出杀血吸虫缺陷。最近，我们的研究小组已经证明，对羟基苯甲酸钾盐（PS-UA）对曼氏血吸虫的成虫对具有杀血吸虫活性。因此，本研究首次报道了 PS-UA 对不同发育阶段的曼氏血吸虫（尾蚴和幼蚴）的体外活性。作为杀血吸虫参数，我们通过扫描电子显微镜（SEM）评估了运动性、死亡率、蠕虫细胞活力和表皮变化。暴露 3 小时后，PS-UA 在浓度为 100 和 50 μM 时对尾蚴具有致死性，而浓度为 25 和 12.5 μM 时，死亡率分别为 38%和 18%，运动性分别变化 62%和 24%。然而，对于尾蚴，浓度为 25 μM 时，分别在 6 小时和 12 小时后达到 90%和 100%的死亡率。在 12.5 μM 的浓度下，间隔 12 和 24 小时的死亡率分别为 68%和 100%。对于幼蚴，暴露 3 小时后，浓度为 200 和 100 μM 时分别引起 57%和 27%的死亡率。12 小时和 24 小时后，这些浓度分别导致 90%和 100%和 47%和 60%的死亡率。暴露 24 小时后，浓度为 50 和 25 μM 时，运动性分别变化 80%和 30%。然而，在 12.5 μM 的浓度下，没有观察到变化。此外，PS-UA 分别在浓度为 100 和 200 μM 时将幼蚴的细胞活力降低了 50.98%和 85.87%。在蠕虫的两个阶段和不同的暴露间隔下，PS-UA 引起了诸如背腹收缩、脱皮、肿胀、水疱、侵蚀、皮下组织暴露和表皮崩解等变化。根据结果，PS-UA 对尾蚴和幼蚴的运动性和死亡率的改变是浓度和时间依赖性的，即使在低浓度下，PS-UA 也能够导致蠕虫表皮的深刻超微结构变化。PS-UA 是曼氏血吸虫病防治的有希望的候选药物。
