Edaravone Protects Trophoblast Cells From Hypoxic Injury in Preeclampsia: Inhibition of the PI3K/AKT Pathway as a Promising Therapeutic Approach

EDA protected trophoblasts against hypoxic injury by inhibiting the PI3K/AKT pathway, suggesting that it may serve as a promising therapeutic option for PE.

Placenta tissues from pregnant women, with or without PE, were collected, and levels of hypoxia-inducible factor (HIF-1α), P-AKT, AKT, and PI3K proteins were analyzed using Western blotting. An in vitro anoxia model was established by treating the human trophoblast cell line HTR-8/SVneo with cobalt chloride (CoCl2). Standard techniques were employed to measure proliferation, apoptosis, and reactive oxygen species (ROS) production rates in the anoxic cells, with and without EDA treatment.

Preeclampsia (PE) is a multifaceted medical condition that manifests during pregnancy, characterized by hypertension and damage to multiple organs. In PE, the placenta's impaired functionality leads to continuous hypoxia in placental tissues, which is considered the primary cause of the condition. Inhibition of hypoxia-induced injury in trophoblast cells presents a potential therapeutic strategy for PE. Edaravone (EDA) is a potent antioxidant with proven efficacy against various diseases and injuries, yet its impact on PE requires further exploration.

HIF-1α, P-AKT, AKT, and PI3K protein levels were significantly elevated in the placenta of the PE group compared with the control group. EDA mitigated the CoCl2-induced decrease in HTR-8/SVneo cell viability and reduced apoptosis and ROS production. Furthermore, EDA counteracted the activation of the PI3K/AKT pathway in CoCl2-treated trophoblasts.