Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo

文献类型： 外文期刊

第一作者： Mo, Jiao

作者： Mo, Jiao;Liu, Siyang;Zeng, Qingyuan;Cai, Minghao;Liu, Zhendi;Zhang, Jili;Fang, Jingjing;Zhang, Jili;Si, Hongfei;Zhang, Jiyu;Zhang, Jili;Zhang, Jili

作者机构： Ningbo Univ, Sch Med, Ningbo, Peoples R China;Ningbo Univ, Affiliated Hosp, Med Sch, Intens Care Unit, Ningbo, Peoples R China;Jinan Univ, Coll Pharm, Guangzhou, Peoples R China;Chinese Acad Agr Sci, Lanzhou Inst Husb & Pharmaceut Sci, Beijing, Peoples R China;Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China

关键词： HQNO; Toxoplasma gondii; Invasion; Proliferation; Pharmacokinetics; In vivo; TEM

期刊名称：INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE （ 2022影响因子：4.0； 五年影响因子：3.7 ）

ISSN： 2211-3207

年卷期： 2023 年 21 卷

页码：

收录情况： SCI

摘要： Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited T. gondii invasion and proliferation with an EC50 of 0.995 mu M. Pharmacokinetic experiments showed that the C-max of HQNO (20 mg/kg.bw) was 3560 +/- 1601 ng/mL (13.73 mu M) in healthy BALB/c mouse plasma with no toxicity in vivo. Moreover, HQNO induced a significant decrease in the parasite burden load of T. gondii in mouse peritoneum. TEM revealed alterations in the mitochondria of T. gondii. Further assays verified that HQNO also decreased the mitochondrial membrane potential (Delta Psi m) and ATP levels and enhanced the level of reactive oxygen species (ROS) in T. gondii. Hence, HQNO exerted anti-T. gondii activity, which may be related to the damage to the mitochondrial electron transport chain (ETC).

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序