Molefe Nthatisi Innocentia, Yamasaki Shino, Macalanda Adrian Miki C, Suganuma Keisuke, Watanabe Kenichi, Xuan Xuenan, Inoue Noboru
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada, Obihiro, Hokkaido, 080-8555, Japan.
Research Center for Global Agromedicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada, Obihiro, Hokkaido, 080-8555, Japan.
Parasitol Res. 2017 Sep;116(9):2407-2415. doi: 10.1007/s00436-017-5542-7. Epub 2017 Jul 4.
Animal trypanosomosis is a devastating parasitic disease that is of economic importance to livestock production. The infection includes animal African trypanosomosis, surra, and dourine. The treatment is based solely on few compounds that were discovered decades ago and which are associated with severe toxicity. Furthermore, it is likely that the parasite has developed resistance towards them. Thus, there is an urgent need for new, accessible, and less toxic drugs. Azithromycin is an antibiotic with documented efficacy against Toxoplasma, Babesia, and Plasmodium. The current study investigated its effects against animal trypanosomes. An in vitro system was used to determine the trypanocidal effects of azithromycin against Trypanosoma congolense, Trypanosoma brucei brucei, and Trypanosoma evansi, and cytotoxicity in Madin-Darby bovine kidney (MDBK) and NIH 3T3 cells. Furthermore, the trypanocidal effects of azithromycin were investigated in T. congolense-infected mice. In vitro, azithromycin had an IC of 0.19 ± 0.17; 3.69 ± 2.26; 1.81 ± 1.82 μg/mL against T. congolense, T. b. brucei, and T. evansi, respectively. No cytotoxic effects were observed in MDBK and NIH 3T3 cells. The efficacy of orally administered azithromycin was investigated in short-term and long-term treatment protocols. Although the short-term treatment protocol showed no curative effects, the survival rate of the mice was significantly prolonged (p < 0.001) in comparison to the control group. The long-term treatment yielded satisfying curative effects with doses of 300 and 400 mg/kg achieving 80 and 100% survival, respectively. In conclusion, long-term oral azithromycin treatment has trypanocidal effects against T. congolense.
动物锥虫病是一种具有毁灭性的寄生虫病，对畜牧业生产具有重要经济意义。该感染包括动物非洲锥虫病、苏拉病和马媾疫。治疗仅基于几十年前发现的少数几种化合物，这些化合物具有严重毒性。此外，寄生虫很可能已对它们产生耐药性。因此，迫切需要新的、可获取且毒性较小的药物。阿奇霉素是一种抗生素，已证明对弓形虫、巴贝斯虫和疟原虫有效。本研究调查了其对动物锥虫的作用。使用体外系统测定阿奇霉素对刚果锥虫、布氏布氏锥虫和伊氏锥虫的杀锥虫作用，以及对马德堡-达比牛肾（MDBK）细胞和NIH 3T3细胞的细胞毒性。此外，还在感染刚果锥虫的小鼠中研究了阿奇霉素的杀锥虫作用。在体外，阿奇霉素对刚果锥虫、布氏布氏锥虫和伊氏锥虫的半数抑制浓度（IC）分别为0.19±0.17；3.69±2.26；1.81±1.82μg/mL。在MDBK细胞和NIH 3T3细胞中未观察到细胞毒性作用。通过短期和长期治疗方案研究了口服阿奇霉素的疗效。虽然短期治疗方案未显示出治愈效果，但与对照组相比，小鼠的存活率显著延长（p<0.001）。长期治疗产生了令人满意的治愈效果，300和400mg/kg剂量分别实现了80%和100%的存活率。总之，长期口服阿奇霉素治疗对刚果锥虫具有杀锥虫作用。
