Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, 110866Shengyang, China.
College of Food Science, Shenyang Agricultural University, Dongling Road 120, 110866Shengyang, China.
Parasitology. 2021 Jan;148(1):122-128. doi: 10.1017/S0031182020002036. Epub 2020 Oct 22.
Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L-1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.
刚地弓形虫是一种专性细胞内寄生的原虫，几乎可以感染所有的温血动物，包括人类，导致弓形体病。目前，人类弓形虫病的有效治疗方法是磺胺嘧啶和乙胺嘧啶的联合用药。然而，这两种药物在宿主中都有严重的副作用和毒性。因此，迫切需要发现新的抗弓形虫药物，具有高效力、低毒或无毒副作用。我们的研究结果表明，青蒿琥酯通过抑制其在体外 Vero 细胞中的增殖而对 T. gondii 发挥作用，而对 Vero 细胞没有毒性（P ≤ 0.01）。青蒿琥酯在浓度为 50μg L-1 时，可使感染弓形虫的小鼠存活时间延长 3 天，比阴性对照（仅用磷酸盐缓冲盐水处理）长，并且在体内减少了小鼠组织中的寄生虫负荷（P ≤ 0.01；P ≤ 0.05）。此外，在高剂量青蒿琥酯处理的小鼠中观察到干扰素 γ（IFN-γ）的产生显著增加（P ≤ 0.01），而在低剂量青蒿琥酯处理的小鼠中白细胞介素 10（IL-10）和 IL-4 水平增加（P ≤ 0.01）。结果表明，青蒿琥酯可能是治疗弓形体病的一种有前途的药物，在进一步的研究中应进行更多关于青蒿琥酯保护机制的实验。
