Determination of lumefantrine as an effective drug against Toxoplasma gondii infection - in vitro and in vivo study.

Determination of lumefantrine as an effective drug against Toxoplasma gondii infection - in vitro and in vivo study.
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苯芴醇作为对抗弓形虫感染的有效药物的测定→体外和体内研究

DOI:
10.1017/s0031182020002036
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发表时间:
2021-01
期刊:
影响因子:
2.4
通讯作者:
Yang N
Yang N
中科院分区:
医学2区
文献类型:
--
作者:
Wang D;Xing M;El-Ashram S;Ding Y;Zhang X;Sang X;Feng Y;Chen R;Wang X;Jiang N;Chen Q;Yang N

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刚地弓形虫是一种专性细胞内原生动物寄生虫,它可以感染包括人类在内的几乎所有温血动物,导致弓形虫病。目前,治疗人类弓形虫病的有效方法是磺胺嘧啶与乙胺嘧啶联用。然而,这两种药物在宿主体内都有严重的副作用和毒性。因此,迫切需要发现新的抗t抗体。效力高、副作用少或无副作用的弓形虫药物。本研究结果提示,鲁苯曲明通过抑制弓形虫在体外Vero细胞内的增殖发挥抗弓形虫活性,但对Vero细胞无毒性作用(P≤0.01)。在50 μg L−1浓度下,与阴性对照(仅用磷酸盐缓冲盐水处理)相比,氟苯曲明可延长弓形虫感染小鼠的死亡时间3 d,并可降低小鼠体内组织中的寄生虫负担(P≤0.01;P≤0.05)。此外,高剂量发光芳碱处理小鼠的干扰素γ (IFN-γ)产生显著增加(P≤0.01),而低剂量发光芳碱处理小鼠的白细胞介素10 (IL-10)和IL-4水平升高(P≤0.01)。结果表明,氨苯曲明可能是治疗弓形虫病的一种很有前景的药物,对氨苯曲明的保护机制有待进一步的实验研究。
Abstract 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.
DOI: 10.1371/journal.pone.0121647
发表时间: 2015
期刊: PloS one
影响因子: 3.7
作者:
El-Ashram S;Sun X;Yin Q;Liu X;Suo X
通讯作者: Suo X
DOI: 10.1186/1475-2875-13-189
发表时间: 2014-05-25
期刊: Malaria journal
影响因子: 3
作者:
Dormoi J;Savini H;Amalvict R;Baret E;Pradines B
通讯作者: Pradines B
DOI: 10.1186/1475-2875-11-347
发表时间: 2012-10-19
期刊: Malaria journal
影响因子: 3
作者:
Eibach D;Ceron N;Krishnalall K;Carter K;Bonnot G;Bienvenu AL;Picot S
通讯作者: Picot S