Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles Oliveira, 201, 14404600, Franca, SP, Brazil.
Parasitol Res. 2013 Jan;112(1):431-6. doi: 10.1007/s00436-012-3048-x. Epub 2012 Jul 27.
Nifurtimox and benznidazole, medications currently used for the treatment of the Chagas disease, are not always successful. We determine whether (-)-cubebin and (-)-hinokinin could be used as alternative drugs for the treatment of parasitic infections by Trypanosoma cruzi. To this end, male BALB/c mice were treated with both drugs, and the nuclear parameters (largest diameter, smallest diameter, and perimeter) were determined from slides prepared from the spleen, liver, and heart. The cytotoxicity of the substances was determined after 24-h treatment. Results revealed increased cell nuclei in untreated infected animals as compared to uninfected mice. The values obtained for infected animals treated with (-)-cubebin and (-)-hinokinin were close to those observed for uninfected mice. For the spleen, perimeter values of 10.85 μm (p < 0.01) and 10.90 μm (p < 0.05) were obtained for mice treated with (-)-cubebin 50 mg/kg and (-)-hinokinin 20 mg/kg, respectively, whereas untreated infected animals furnished a perimeter of 11.76 μm. As for the liver, perimeter values of 19.06 μm (p < 0.01) and 18.61 μm (p < 0.001) were achieved for mice treated with (-)-cubebin 50 mg/kg and (-)-hinokinin 20 mg/kg, respectively, whereas a perimeter of 18.54 μm was obtained for untreated infected animals. The cytotoxicity assays demonstrated that (-)-cubebin and (-)-hinokinin does not display toxicity. Therefore, (-)-cubebin and (-)-hinokinin are promising therapeutic agents and could be used in future clinical studies concerning treatment of the Chagas disease. Even if the karyometry is not used frequently, it can complement other methods, such as PCR, and furthermore, it is a simple method which is easily possible to analyze the activity of substances in the tissues of treated infected animals compared to uninfected animals.
硝呋替莫和苯并硝呋酮是目前用于治疗恰加斯病的药物，但并不总是有效。我们确定 (-)-古巴宾和 (-)-扁柏素是否可作为治疗克氏锥虫寄生虫感染的替代药物。为此，雄性 BALB/c 小鼠用这两种药物进行治疗，并从脾脏、肝脏和心脏制备的载玻片上确定核参数（最大直径、最小直径和周长）。在 24 小时治疗后，测定物质的细胞毒性。结果表明，与未感染的小鼠相比，未经处理的感染动物的细胞核增大。用 (-)-古巴宾和 (-)-扁柏素处理感染动物所获得的值接近未感染的小鼠。对于脾脏，用 50mg/kg 的 (-)-古巴宾和 20mg/kg 的 (-)-扁柏素治疗的小鼠的周长值分别为 10.85μm(p<0.01)和 10.90μm(p<0.05)，而未经处理的感染动物的周长值为 11.76μm。对于肝脏，用 50mg/kg 的 (-)-古巴宾和 20mg/kg 的 (-)-扁柏素治疗的小鼠的周长值分别为 19.06μm(p<0.01)和 18.61μm(p<0.001)，而未经处理的感染动物的周长值为 18.54μm。细胞毒性测定表明，(-)-古巴宾和 (-)-扁柏素没有毒性。因此，(-)-古巴宾和 (-)-扁柏素是很有前途的治疗药物，可用于未来治疗恰加斯病的临床研究。即使核测量法不常使用，它也可以补充其他方法，如 PCR，此外，与未感染的动物相比，它是一种简单的方法，更容易分析治疗感染动物组织中物质的活性。
