Edaravone protects against cobalt chloride-induced dysfunctions in apoptosis and invasion in trophoblast cells.

Abstract

This study was performed to investigate the effects of edaravone on hypoxia-induced trophoblast cell proliferation, apoptosis, and invasion. The trophoblast cell line HTR-8 (H8) was treated with cobalt chloride (CoCl2 ) with or without a 1-hr edaravone pretreatment, followed by assessment of intracellular reactive oxygen species (ROS) levels, cell proliferation, apoptosis, migration, and invasion. Metrics of apoptosis included measurement of cysteine-aspartic acid protease 3 (CASP3) activity as well as BAX and BCL2 expression. Migration and invasion phenotypes were complemented with expression analysis of matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2) at the transcript and protein levels. CoCl2 inhibited the proliferation of H8 cells, promoted apoptosis, and up-regulated CASP3 activation and BAX expression while inhibiting BCL2 expression. CoCl2 treatment also reduced the invasiveness of H8 cells by inhibiting MMP2 activity. Edaravone significantly increased H8 cell proliferation; inhibited apoptosis by down-regulating CASP3 activation and BAX production while promoting BCL2 stability; and ameliorated the migration and invasion phenotypes associated with CoCl2 treatment. These results suggest that edaravone may rescue hypoxia-induced abnormalities in H8 cell proliferation, apoptosis, and invasion, thereby protecting the trophoblast lineage against hypoxia. Mol. Reprod. Dev. 83: 576-587, 2016. © 2016 Wiley Periodicals, Inc.