Kamau S W, Hurtado M, Müller-Doblies U U, Grimm F, Nunez R
Institute of Parasitology, University of Zurich, Switzerland.
Cytometry. 2000 Aug 1;40(4):353-60.
Leishmaniasis is a major tropical and subtropical parasitic disease. Sodium stibogluconate, N-methyl -D-glucamine antimoniate, amphotericin B, pentamidine, and ketoconazole are drugs used to treat this disease. Some of these drugs cause severe adverse side effects and treatment failures are common. Allopurinol, a purine analog, has been used to treat leishmaniasis, alone or combined with the previously mentioned drugs. Low cost, ease of administration (oral), and lack of toxicity make allopurinol a particularly appealing candidate.
The effect of allopurinol on Leishmania infantum (MCAN/ES/89/IPZ229/1/89, zymodeme MON1) wild-type promastigotes (wt-p229), and an altered form of these promastigotes (allo-p229) resulting from long term in vitro exposure to allopurinol, was determined by [(3)H]-thymidine incorporation assays and by diverse flow cytometric approaches.
Allopurinol arrested the proliferative capacity of wt-p229 promastigotes, reduced the proportion of viable cells, and decreased their total protein content. In contrast, allo-p229 promastigote proliferation was only slightly decelerated and the proportion of viable cells and the protein content were not affected by the allopurinol treatment.
The flow cytometry approach allowed us to demonstrate differences in allopurinol susceptibility of the two promastigote forms, expanding the spectrum of flow cytometry applications in studies of parasite resistance.
利什曼病是一种主要的热带和亚热带寄生虫病。葡萄糖酸锑钠、葡甲胺锑酸盐、两性霉素B、喷他脒和酮康唑是用于治疗该病的药物。其中一些药物会引起严重的不良反应，治疗失败很常见。嘌呤类似物别嘌呤醇已被用于治疗利什曼病，单独使用或与上述药物联合使用。低成本、易于给药（口服）以及无毒性使别嘌呤醇成为一个特别有吸引力的候选药物。
通过[³H] - 胸腺嘧啶核苷掺入试验和多种流式细胞术方法，测定别嘌呤醇对婴儿利什曼原虫（MCAN/ES/89/IPZ229/1/89，酶谱型MON1）野生型前鞭毛体（wt - p229）以及长期体外暴露于别嘌呤醇后产生的这些前鞭毛体的一种改变形式（allo - p229）的影响。
别嘌呤醇抑制了wt - p229前鞭毛体的增殖能力，降低了活细胞比例，并减少了它们的总蛋白含量。相比之下，allo - p229前鞭毛体的增殖仅略有减速，活细胞比例和蛋白含量不受别嘌呤醇处理的影响。
流式细胞术方法使我们能够证明两种前鞭毛体形式在别嘌呤醇敏感性上的差异，扩大了流式细胞术在寄生虫抗性研究中的应用范围。
