Araújo Neusa, Mattos Ana Carolina Alves de, Sarvel Ana Karine, Coelho Paulo Marcos Zech, Katz Naftale
Laboratório de Esquistossomose, Instituto René Rachou, Fiocruz, Belo Horizonte, MG, Brasil.
Mem Inst Oswaldo Cruz. 2008 Aug;103(5):450-4. doi: 10.1590/s0074-02762008000500007.
The activity of lovastatin associated with oxamniquine or praziquantel against schistosomiasis mansoni was evaluated in mice infected with Schistosoma mansoni. Forty days after infection, mice were treated with lovastatin, 400 mg/kg for five consecutive days by oral route, and on the last day of this sequence with 50 mg/kg oxamniquine or with 200 mg/kg praziquantel, both by oral route, single dose. Fifteen days later, the animals were perfused in parallel with an untreated control group. Studies were carried out in vitro, using lovastatin in culture medium containing S. mansoni worms proceeding from experimentally infected mice. In the in vivo trials, the association of lovastatin with oxamniquine or praziquantel did not show any additive action, but there were oogram changes when lovastatin was associated with oxamniquine. In vitro lovastatin was able to interrupt the maturation of S. mansoni eggs, which remained at the 1st or 2nd stages, depending on the dose used. The total number of morphologically dead eggs found in culture of worms exposed to 2 microg/ml or 4 microg/ml concentrations of lovastatin was significantly higher than the number of viable eggs. Using the probe Hoescht 33258 it was observed that 70% of the eggs considered morphologically viable in the treated groups (against 16% in the control group) were labeled, indicating that the majority of the viable eggs had membrane permeability increased due to lovastatin action.
在感染曼氏血吸虫的小鼠中评估了洛伐他汀与奥沙尼喹或吡喹酮联合抗曼氏血吸虫病的活性。感染后40天,小鼠经口服给予洛伐他汀,剂量为400mg/kg,连续5天,在该给药序列的最后一天,分别经口服单剂量给予50mg/kg奥沙尼喹或200mg/kg吡喹酮。15天后,对动物进行灌注,并与未治疗的对照组平行进行研究。在体外实验中,将洛伐他汀用于含有来自实验感染小鼠的曼氏血吸虫虫体的培养基中。在体内试验中,洛伐他汀与奥沙尼喹或吡喹酮联合使用未显示出任何相加作用,但洛伐他汀与奥沙尼喹联合使用时虫卵图谱有变化。在体外,洛伐他汀能够阻断曼氏血吸虫虫卵的成熟,根据所用剂量不同,虫卵停留在第1或第2阶段。在暴露于2μg/ml或4μg/ml洛伐他汀浓度的虫体培养物中发现的形态学上死亡的虫卵总数显著高于活虫卵数。使用Hoechst 33258探针观察到,在治疗组中被认为形态学上存活的虫卵中有70%被标记(对照组为16%),这表明由于洛伐他汀的作用,大多数存活虫卵的膜通透性增加。