Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
Parasitol Res. 2012 Oct;111(4):1807-16. doi: 10.1007/s00436-012-3028-1. Epub 2012 Jul 15.
The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dose-titration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg(-1) day(-1)) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological and immunological parameters were analyzed. Mice treated with the AbM presented a 60% reduction in the inflammation of infected footpads as compared to untreated control-infected mice. Moreover, in the treated mice, as compared to the untreated controls, approximately 60 and 66% reductions could be observed in the parasite burdens of the footpad and draining lymph nodes, respectively. In addition, no parasites could be detected in the spleen of treated mice at week 14 postinfection. These treated animals produced significantly higher levels of interferon gamma (IFN-γ) and nitric oxide (NO), higher levels of parasite-specific IgG2a isotype antibodies, and lower levels of interleukin (IL)-4, and IL-10 in the spleen and lymph node cell cultures than did the controls. Differences could be observed by comparing animals treated with AbM to those treated with AmpB, as indicated by a significant reduction in tissue parasitism, higher levels of IFN-γ and NO, and lower levels of IL-4 and IL-10, as well as by a decreased hepatic toxicity. In conclusion, the present study's data show that the A. blazei Murill water extract presents a high potential for the treatment of leishmaniasis, although additional studies on mice, as well as on other mammal hosts, are warranted in an attempt to determine this extract's true efficacy as compared to other known therapeutic products.
治疗性替代疗法治疗利什曼病已受到广泛关注。本研究旨在研究巴西蘑菇水提取物(AbM)治疗感染利什曼原虫亚马逊亚种的 BALB/c 小鼠的疗效。首先,进行了剂量滴定曲线实验。考虑到产品的每日给药,能够在感染动物中产生最有效结果的最明确浓度为 100mg/kg/天。在这种情况下,AbM 通过口服途径给药,从感染后第 0 天开始给药,持续 20 天。另外一些动物通过腹腔途径用两性霉素 B(AmpB,5mg/kg/天)治疗相同时间,而对照组则给予蒸馏水。感染后 14 周时对动物进行评估,分析寄生虫学和免疫学参数。与未治疗的感染对照组相比,用 AbM 治疗的小鼠感染足垫的炎症减少了 60%。此外,与未治疗的对照组相比,在治疗组小鼠中,足垫和引流淋巴结中的寄生虫负荷分别减少了约 60%和 66%。此外,在感染后 14 周时,未在治疗组小鼠的脾脏中检测到寄生虫。与对照组相比,这些治疗组动物在脾和淋巴结细胞培养物中产生了更高水平的干扰素 γ(IFN-γ)和一氧化氮(NO),更高水平的寄生虫特异性 IgG2a 同种型抗体,以及更低水平的白细胞介素(IL)-4 和 IL-10。与用 AmpB 治疗的动物相比,用 AbM 治疗的动物的组织寄生虫感染显著减少,IFN-γ 和 NO 水平更高,IL-4 和 IL-10 水平更低,并且肝毒性降低,这表明存在差异。总之,本研究的数据表明,巴西蘑菇水提取物具有治疗利什曼病的巨大潜力,尽管需要在小鼠以及其他哺乳动物宿主中进行更多的研究,以确定与其他已知治疗产品相比,该提取物的真正疗效。