Characterization of the Activities of Vorinostat Against Toxoplasma gondii

Toxoplasma gondii is a globally widespread pathogen of significant veterinary and medical importance, causing abortion or congenital disease in humans and other warm-blooded animals. Nevertheless, the current treatment options are restricted and sometimes result in toxic side effects. Hence, it is essential to discover drugs that demonstrate potent anti-Toxoplasma activity. Herein, we found that vorinostat, a pan-HDAC inhibitor, exhibited an IC₅₀ value of 260.1 nM against the T. gondii RH strain and a selectivity index (SI) > 800 with respect to HFF cells. Vorinostat disrupted the entire lytic cycle of T. gondii in vitro. Proteome analysis indicated that vorinostat remarkably perturbed the protein expression of T. gondii, and proteins involved in "DNA replication" and "membrane" were significantly dysregulated. Furthermore, we found that vorinostat significantly enhanced ROS production and induced parasite apoptosis. Importantly, vorinostat could prolong survival in a murine model. Our findings reveal that vorinostat is effective against T. gondii both in vitro and in vivo, suggesting its potential as a therapeutic option for human toxoplasmosis.