Caffeic acid reduces Toxoplasma gondii proliferation in human extravillous trophoblast cells (HTR8/SVneo) through induction of pro-inflammatory cytokines and a death process suggestive of apoptosis.

BACKGROUND Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a public health problem, especially in congenital infections. Current treatments, with spiramycin or pyrimethamine and sulfadiazine, are highly toxic, prompting the search for effective and safe natural alternatives.

OBJECTIVE This study evaluated the in vitro effect of caffeic acid (CA) on human extravillous trophoblast cells (HTR8/SVneo) infected by T. gondii.

METHODS The microbicidal and metabolic activity of CA against free tachyzoites was analyzed, in addition to its immunological and anti-Toxoplasma action in infected trophoblast cells.

RESULTS The compound was able to reduce the viability of tachyzoites (IC50 5 μg/mL) without any toxicity to the trophoblast cells (CC50 1950 μg/mL); in addition, it reduced the proliferation and infection by tachyzoites at all concentrations tested (5-50 μg/mL). CA also induced changes to the parasite's morphology, including mitochondrial integrity loss, increased production of reactive oxygen species, nitric oxide, exposure to phosphatidylserine and loss of plasmatic membrane integrity, characterizing an apoptosis-like process. Furthermore, there was an increase in interleukins interleukin-1 beta (IL-1β), macrophage migration inhibitory factor (MIF) and transforming growth factor beta (TGF-β) in the T. gondii infected HTR8/SVneo cells.

CONCLUSION CA is a potential candidate for further research aimed at the development of novel therapies for congenital toxoplasmosis.