Determination of lumefantrine as an effective drug against Toxoplasma gondii infection - in vitro and in vivo study.
Dawei WangMengen XingSaeed A El-AshramYingying DingXiao ZhangXiaoyu SangYing FengRan ChenXinyi WangNing JiangQijun ChenNa YangPublished in: Parasitology (2020)
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.
Keyphrases
- toxoplasma gondii
- low dose
- high dose
- induced apoptosis
- high fat diet induced
- signaling pathway
- cell cycle arrest
- gene expression
- dendritic cells
- immune response
- emergency department
- type diabetes
- high throughput
- adipose tissue
- cell proliferation
- cell death
- mass spectrometry
- drug induced
- metabolic syndrome
- stem cell transplantation
- wild type
- high resolution
- pi k akt
- tandem mass spectrometry