Corpas-López V, Merino-Espinosa G, Acedo-Sánchez C, Díaz-Sáez V, Navarro-Moll M C, Morillas-Márquez F, Martín-Sánchez J
Departamento de Parasitología, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja, Granada, 18011, Spain.
ANLAVE Laboratorio de Análisis Veterinario, Avenida de Pulianas 15, 18013, Granada, Spain.
Vet Res Commun. 2018 Jun;42(2):121-130. doi: 10.1007/s11259-018-9714-4. Epub 2018 Feb 16.
The use of natural products is a promising approach for treating visceral leishmaniosis. (-)-α-Bisabolol is a sesquiterpene that have been proved active in vivo on Leishmania infantum-infected mice without showing toxicity. A single-centre, parallel-group, randomized, exploratory study was designed to assess its efficacy in a canine leishmaniosis model involving naturally infected dogs. In this clinical trial, 12 dogs were allocated into two groups and were treated with either meglumine antimoniate (100 mg/kg) through subcutaneous route or (-)-α-bisabolol (30 mg/kg) through oral route for two treatment series of 30 days, separated by a 30-day interval. A 4-month follow-up period was established as well. Parasite loads in bone marrow, lymph node and blood were estimated through quantitative PCR. Antibody titres were determined through immunofluorescence antibody test and cytokine expression values were estimated through real-time reverse transcription-PCR. Treatment safety was assessed through the evaluation of weight, gastrointestinal alterations and hematological and biochemical parameters in blood. Analyses were performed before and after treatment, and after a 4-months follow-up period. Treatment with the sesquiterpene was effective at decreasing parasite loads and increasing gamma-interferon expression level. Dogs treated with (-)-α-bisabolol did not show any toxicity sign. These results were better than those obtained using the reference drug, meglumine antimoniate. The natural compound seemed to induce a Th1 immune response that led to parasitological and clinical improvement without showing any safety issue, suggesting a high potential for the treatment of canine and human visceral leishmaniosis.
使用天然产物是治疗内脏利什曼病的一种有前景的方法。（-）-α-红没药醇是一种倍半萜，已被证明在体内对感染婴儿利什曼原虫的小鼠具有活性，且无毒性。一项单中心、平行组、随机、探索性研究旨在评估其在涉及自然感染犬的犬利什曼病模型中的疗效。在这项临床试验中，12只犬被分为两组，分别通过皮下途径接受葡甲胺锑酸盐（100mg/kg）治疗或通过口服途径接受（-）-α-红没药醇（30mg/kg）治疗，进行两个为期30天的治疗周期，中间间隔30天。还建立了4个月的随访期。通过定量PCR估计骨髓、淋巴结和血液中的寄生虫载量。通过免疫荧光抗体试验测定抗体滴度，并通过实时逆转录PCR估计细胞因子表达值。通过评估体重、胃肠道改变以及血液中的血液学和生化参数来评估治疗安全性。在治疗前、治疗后以及4个月随访期后进行分析。倍半萜治疗在降低寄生虫载量和提高γ-干扰素表达水平方面有效。用（-）-α-红没药醇治疗的犬未表现出任何毒性迹象。这些结果优于使用参考药物葡甲胺锑酸盐所获得的结果。这种天然化合物似乎诱导了Th1免疫反应，从而导致寄生虫学和临床改善，且未显示任何安全问题，表明其在治疗犬和人类内脏利什曼病方面具有很高的潜力。
