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With no causative treatment available, diagnosed patients have limited therapeutic options, putting them at risk for pregnancy complications. The induction of oxidative stress by ROS\u2014one of the major contributors in PE pathogenesis\u2014causes downstream signaling and production of anti-angiogenic factors, such as sFLT1 and sEng. The anti-angiogenic factors may cause endothelial and trophoblast dysfunction, contributing to the development of hypertension, proteinuria, and in severe cases, eclampsia. To target placental oxidative stress, we developed and evaluated an organofluorine hydrazone antioxidant, HY-12, in vitro. Human trophoblast (HTR8\/SVneo) cells were incubated with hydrogen peroxide to induce oxidative stress and act as a model of PE. The goal of the study was to assess the efficacy of HY-12 and its ability to reduce cell injury, mitochondrial stress, and anti-angiogenic response. In our human trophoblast-based assays, pre-treatment with HY-12 reduced mitochondrial-derived ROS production in cells exposed to hydrogen peroxide, proving its ability to alleviate the oxidative stress associated with the pathogenesis of PE. HY-12 reduced HIF1A expression and sFLT1 protein expression in H2O2-exposed HTR8 cells. Furthermore, HY-12 improved the activity of the mitochondrial electron chain enzyme cytochrome C oxidase (COX) in the hydrogen-peroxide-treated HTR8\/SVneo cells, which is a promising attribute of the compound. In reducing placental trophoblast oxidative stress, HY-12 shows promise as a potential treatment of preeclampsia. In vivo studies are warranted to further determine the efficacy of this compound.<\/jats:p>","DOI":"10.3390\/cimb47090680","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:53Z","timestamp":1756080593000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitigating Oxidative Stress and Anti-Angiogenic State in an In Vitro Model of Preeclampsia by HY-12, an Organofluorine Hydrazone Antioxidant"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-5728","authenticated-orcid":false,"given":"Zsuzsanna K.","family":"Zsengell\u00e9r","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Mastyugin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrianna R.","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"},{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6373-2257","authenticated-orcid":false,"given":"Bernadett","family":"Vlocsk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coryn","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Pintye","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9ka Eszter","family":"Sziva","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN, Semmelweis University, 1082 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saira","family":"Salahuddin","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN, Beth Israel Lahey Health, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-1283","authenticated-orcid":false,"given":"Brett C.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of OB\/GYN, Mt Auburn Hospital, Boston, MA 02138, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-1984","authenticated-orcid":false,"given":"Marianna","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9la","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","unstructured":"American College of Obstetricians and Gynecologists (2019). 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