Evaluating oxidative stress targeting treatments in in vitro models of placental stress relevant to preeclampsia

• DOI: 10.3389/fcell.2025.1539496
• Publication Date: 2025-02-28T07:25:01Z
• Authors: Dinara Afrose; Matt D. Johansen; Valentina Nikolic; Natasa Karadzov O...; Zeljko Mikovic; Milan Stefanovic; Zoran Cakic; Philip M. Hansbro; Lana McClements
• Keywords: preeclampsia; placenta; QH301-705.5; oxidative stress; pregnancy; resveratrol; Biology (General); trophoblast cells

Preeclampsia is a complex pregnancy disorder characterized by the new onset of hypertension and organ dysfunction, often leading to significant maternal fetal morbidity mortality. Placental dysfunction hallmark feature preeclampsia, which caused inappropriate trophoblast cell function in association with oxidative stress, inflammation and/or pathological hypoxia. This study explores role stress cell-based models mimicking preeclamptic placenta evaluates potential therapeutic strategies targeting these mechanisms. Uric acid (UA) malondialdehyde (MDA) concentrations were measured human plasma from women preeclampsia (n = 24) or normotensive controls 14) using colorimetric assays. Custom-made first trimester line, ACH-3P, was exposed various preeclampsia-like stimuli including hypoxia mimetic (dimethyloxalylglycine DMOG, 1 mM), (tumour necrosis factor TNF-α, 10 ng/mL) mitochondria agent, (Rhodamine-6G Rho-6G, μg/mL), ± aspirin (0.5 metformin AD-01 (100 nM) resveratrol (15 µM), for 48 h. Following treatments, UA/MDA, proliferation (MTT), wound scratch cytometric bead, assays, performed. Overall, MDA concentration increased group compared healthy (p < 0.001) whereas UA showed trend towards an increase 0.06); when adjusted differences gestational age at blood sampling, remained became 0.03) significantly correlated preeclampsia. Our 2D vitro model placental as observed mimicked following treatment DMOG 0.0001), TNF-α 0.05) Rho-6G only presence 0.0001) 0.001). Metformin able abrogate DMOG- 0.01), Rho-6G- TNF-α- 0.01) induced UA, 0.05)induced MDA. abrogated 0.001)/DMOG respectively. The also adverse impact on proliferation, migration inflammation, most restored either aspirin, metformin, resveratrol, 0.05). recapitulate response cells stresses, modelling development, demonstrate repurposed treatments.