In vitro and in vivo effects of the phytohormone inhibitor fluridone against Neospora caninum infection

Parasitol Int. 2016 Mar 25. pii: S1383-5769(16)30034-4. doi: 10.1016/j.parint.2016.03.009. [Epub ahead of print]

Ybañez RH¹, Leesombun A², Nishimura M², Matsubara R³, Kojima M⁴, Sakakibara H⁴, Nagamune K⁵, Nishikawa Y⁶.

Neospora caninum causes abortion and stillbirth in cattle. Identification of effective drugs against this parasite remains a challenge. Previous studies have suggested that disruption of abscisic acid (ABA)-mediated signaling in apicomplexan parasites such as Toxoplasma gondii offers a new drug target. In this study, the ABA inhibitor, fluridone (FLU), was evaluated for its action against N. caninum. Production of endogenous ABA within N. caninum was confirmed by ultra-performance liquid chromatography-tandem quadruple mass spectrometry. Subsequently, FLU treatment efficacy was assessed using in vitro. Results revealed that FLU inhibited the growth of N. caninum and T. gondii in vitro (IC₅₀ 143.1±43.96μM and 330.6±52.38μM, respectively). However, FLU did not affect parasite replication at 24h post-infection, but inhibited egress of N. caninum thereafter. To evaluate the effect of FLU in vivo, N. caninum-infected mice were treated with FLU for 15days. FLU treatment appeared to ameliorate acute neosporosis induced by lethal parasite challenge. Together, our data shows that ABA might control egress in N. caninum. Therefore, FLU has potential as a candidate drug for the treatment of acute neosporosis.
Copyright © 2015. Published by Elsevier Ireland Ltd.

KEYWORDS:

Abscisic acid; Fluridone; Neospora caninum

PMID:

27021922

[PubMed - as supplied by publisher]