Grouping, treatment and sampling in vivo test.

作者：J Zhao, Linyan Bao (24239351), Huan Chen (6545), Tenglong Zhao, Dong Tang (104780), Yixi Sun (7371017), Yuqi Zuo (8697102), Jiafu Shang, Yanyan Liu (171941), Xuehui Zhou (24239357), Mengru Zhao, Xiaowei Yang (116246), Liwu Zhang (748578), Guangwei Zhao · 发表于：Figshare · 年份：2026 · DOI：10.1371/journal.pntd.0014454.t001 · 研究领域：Biology、Cell biology、Pharmacology、Microbiology、Biochemistry

Toxoplasma gondii ( T. gondii ) is an obligate intracellular parasite capable of infecting more than 350 species, including humans, livestock, and wildlife. However, available clinical drugs for toxoplasmosis not only cause severe adverse effects but also demonstrate reduced therapeutic efficacy due to the emergence of drug-resistant strains, highlighting the urgent need for novel therapeutic interventions. This study aimed to evaluate the activity of dimethyl itaconate (DI) against T. gondii both in vitro and in vivo and to elucidate its underlying mechanism of action. The in vitro antiparasitic effects of DI were comprehensively investigated using transmission electron microscopy (TEM), plaque assays, quantitative PCR (qPCR), mitochondrial functional assays, ELISA, and transcriptomic profiling. In vivo evaluations were conducted in T. gondii -infected mouse models to assess survival rates, parasite loads, histopathological changes, and oxidative stress modulation. The results revealed that DI-treated tachyzoites exhibited marked organelle disruption, loss of membrane integrity, and activation of autophagy. Plaque assays combined with qPCR analysis consistently demonstrated a dose-dependent suppression of T. gondii proliferation. Notably, DI induced mitochondrial dysfunction, characterized by reduced mitochondrial membrane potential, ATP depletion, and a concomitant increase in reactive oxygen species (ROS) levels, consistent with the transcriptomic profiling d...