National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido 080-8555, Japan; Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro, Hokkaido 080-8555, Japan; Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Parasitol Int. 2021 Apr;81:102260. doi: 10.1016/j.parint.2020.102260. Epub 2020 Nov 29.
The inhibitory efficacies of pyronaridine tetraphosphate (PYR), when used in combination with two novel and potent antibabesial drugs; clofazimine (CF), and MMV396693 were evaluated in the current study against the growth of Babesia bovis, B. caballi, and B. gibsoni in vitro and B. microti in mice. The in vitro study against the selected parasites was performed using combination of PYR with either CF or MMV396693 in ratios ranged from 0.75:0.75 to 0.25:0.25. Combined application of PYR/MMV396693 revealed additive and indifferent interactions against the in vitro growth of all screened Babesia parasites. PYR in combination with CF, achieved indifferent and antagonistic interactions with all used concentration ratios against the in vitro growth of B. bovis and B. caballi. Treatment with PYR-CF combination therapy caused significant inhibition (P < 0.05) of the fluorescence values at days 12, 14, 16, 18, and 22 p.i. in comparison with control mice. Of note, treatment with combination therapy exhibited inhibition in the growth of B. microti (23.16%) greater than those caused by PYR alone. In summary, the obtained results highlight the improvement in the in vivo antibabesial efficacy of PYR when used in combination with CF rather than using PYR alone but such inhibition is still lower than those caused by either DA or CF monotherapies.
本研究评估了吡喃硝唑四磷酸盐（PYR）与两种新型强效抗巴贝斯虫药物氯法齐明（CF）和 MMV396693 联合使用时对牛巴贝斯虫、马巴贝斯虫和吉氏巴贝斯虫体外生长以及小鼠伯氏疏螺旋体的抑制作用。体外研究采用 PYR 与 CF 或 MMV396693 以 0.75:0.75 至 0.25:0.25 的比例联合使用，对选定的寄生虫进行检测。PYR/MMV396693 联合应用对所有筛选的巴贝斯虫体外生长呈相加和无关相互作用。PYR 与 CF 联合应用，对 B. bovis 和 B. caballi 的体外生长，以所有使用浓度比均呈无关和拮抗相互作用。与对照组相比，PYR-CF 联合治疗在感染后第 12、14、16、18 和 22 天导致荧光值显著抑制（P<0.05）。值得注意的是，联合治疗抑制伯氏疏螺旋体的生长（23.16%）大于单独使用 PYR。总之，研究结果表明，与单独使用 PYR 相比，PYR 与 CF 联合使用可提高体内抗巴贝斯虫疗效，但这种抑制作用仍低于单独使用 DHA 或 CF 治疗。
