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

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...

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Autores principales: Wang, Dawei, Xing, Mengen, El-Ashram, Saeed, Ding, Yingying, Zhang, Xiao, Sang, Xiaoyu, Feng, Ying, Chen, Ran, Wang, Xinyi, Jiang, Ning, Chen, Qijun, Yang, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808861/
https://www.ncbi.nlm.nih.gov/pubmed/33087183
http://dx.doi.org/10.1017/S0031182020002036
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author Wang, Dawei
Xing, Mengen
El-Ashram, Saeed
Ding, Yingying
Zhang, Xiao
Sang, Xiaoyu
Feng, Ying
Chen, Ran
Wang, Xinyi
Jiang, Ning
Chen, Qijun
Yang, Na
author_facet Wang, Dawei
Xing, Mengen
El-Ashram, Saeed
Ding, Yingying
Zhang, Xiao
Sang, Xiaoyu
Feng, Ying
Chen, Ran
Wang, Xinyi
Jiang, Ning
Chen, Qijun
Yang, Na
author_sort Wang, Dawei
collection PubMed
description 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.
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spelling pubmed-78088612021-01-22 Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study Wang, Dawei Xing, Mengen El-Ashram, Saeed Ding, Yingying Zhang, Xiao Sang, Xiaoyu Feng, Ying Chen, Ran Wang, Xinyi Jiang, Ning Chen, Qijun Yang, Na Parasitology Research Article 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. Cambridge University Press 2021-01 2020-10-22 /pmc/articles/PMC7808861/ /pubmed/33087183 http://dx.doi.org/10.1017/S0031182020002036 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Dawei
Xing, Mengen
El-Ashram, Saeed
Ding, Yingying
Zhang, Xiao
Sang, Xiaoyu
Feng, Ying
Chen, Ran
Wang, Xinyi
Jiang, Ning
Chen, Qijun
Yang, Na
Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title_full Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title_fullStr Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title_full_unstemmed Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title_short Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study
title_sort determination of lumefantrine as an effective drug against toxoplasma gondii infection – in vitro and in vivo study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808861/
https://www.ncbi.nlm.nih.gov/pubmed/33087183
http://dx.doi.org/10.1017/S0031182020002036
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