数字农科院2.0

Tylvalosin demonstrates anti-parasitic activity and protects mice from acute toxoplasmosis

文献类型： 外文期刊

作者： Weifeng Yuan;Hong Jia;Xiangfang Tang;Ting Xin;Xianyong Liu;Zhanhui Wang;Xing Li;Zhenwen Zhao;Li Liu;Lin Liang;Xinghui Zhao;Zhanzhong Zhao

作者机构：

关键词： Anti-toxoplasma;pp38;PPARδ;SKI-1-SREBP-1;Toxoplasma gondii;Tylvalosin

期刊名称： Life Sciences

ISSN： 0024-3205

年卷期： 2022 年 294 卷

页码：

收录情况： SCIE（2022版）

摘要： Aims: Toxoplasmosis, caused by Toxoplasma gondii (Tg), is one of the most prevalent zoonotic diseases worldwide. Currently, safe and efficient therapeutic options for this disease are still being developed, and are urgently needed. Tylvalosin (Tyl), a broad-spectrum third-generation macrolide, exhibits anti-bacterial, anti-viral, and anti-inflammatory properties. The present study aims to explore the anti-parasitic and immunomodulation activities of Tyl against Tg, and the underlying mechanism. Main methods: Adhesion, invasion, replication, proliferation, plaque, reversibility, immunofluorescence assays and transmission electron microscopy were utilized to determine the anti-Toxoplasma effect of Tyl. With acute toxoplasmosis model and rabies virus-induced brain inflammation model, the anti-toxoplasmosis and immunomodulation activities of Tyl were assessed by colorimetric assay, histopathological and Oil red O staining, and real-time quantitative PCR. The involved molecular mechanisms were investigated by western blotting and immunohistochemical staining. Key findings: Tyl (5 and 10 μg/ml) can inhibit Tg propagation, and damage its ultrastructure irreversibly. The combination of Tyl and Pyrimethamine (Pyr) exhibits a better synergistic effect. Tyl (50 and 100 mg/kg) treatment intraperitoneally can delay mice death and improve survival rate, accompanying the reduced histopathological score and parasite load in the indicated tissues, espically for ileum, liver, spleen, lung and brain. Furthermore, Tg can modulate host phospho-p38 MAPK (pp38), subtilisin/kexin-isozyme-1 (SKI-1)-sterol regulatory element binding protein-1 (SREBP-1) (SKI-1-SREBP-1) pathway and peroxisome proliferators-activated receptor δ (PPARδ), while Tyl is able to reverse these signal pathways close to normal levels. Significance: Our findings indicate that Tyl exhibits anti-Toxoplasma activity and protects mice from acute toxoplasmosis.

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