Ticlopidine is an anti-platelet
drug that inhibits platelet aggregation via the functional alteration of platelet membranes. However, the mechanism underlying the adverse developmental effects of
ticlopidine has not been clearly demonstrated. In this study, we evaluated the developmental toxicity and teratogenicity of
ticlopidine on Xenopus laevis embryos and in human umbilical vein endothelial cells (HUVECs) using a frog embryo
teratogenesis assay-Xenopus (FETAX) and blood and lymph vessel formation assays.
Ticlopidine induced teratogenicity and inhibited growth, as evidenced by mortality rates and embryo lengths, respectively. Moreover,
ticlopidine induced severe
hemorrhages and inhibited both blood and lymph vessel formation by modulating the expression of xMsr and Prox1 in Xenopus embryos. Additionally, Nkx2.5 and Cyl104 levels were perturbed by
ticlopidine exposure, and more extensive aberrations were observed in the liver and heart using whole-mount in situ hybridization. In addition,
ticlopidine reduced branching in HUVECs by blocking the effect of the angiogenic
vascular endothelial growth factor (
VEGF). Results from this study suggest that
ticlopidine is a developmental toxicant and
teratogen and therefore this is a step forward in our understanding of the effects of
ticlopidine during developmental processes.