Vascular endothelial effects of dibutyl phthalate: In vitro and in vivo evidence

Dibutyl phthalate (DBP) is widely used in many consumer and personal care products. Here, we report vascular endothelial response to DBP in three different exposure scenarios: after short-term exposure (24 h) of human endothelial cells (ECs) EA.hy926 to 10−6, 10−5, and 10−4 M DBP, long-term exposure...

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Bibliographic Details
Published in:Chemico-biological interactions 2024-08, Vol.399, p.111120, Article 111120
Main Authors: Stanic, Bojana, Kokai, Dunja, Markovic Filipovic, Jelena, Tomanic, Tamara, Vukcevic, Jelena, Stojkov, Viktor, Andric, Nebojsa
Format: Article
Language:English
Subjects:
Akt
Angiogenesis
Cell migration
Dibutyl phthalate
Endothelial cells
Nitric oxide
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Summary:Dibutyl phthalate (DBP) is widely used in many consumer and personal care products. Here, we report vascular endothelial response to DBP in three different exposure scenarios: after short-term exposure (24 h) of human endothelial cells (ECs) EA.hy926 to 10−6, 10−5, and 10−4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10−9, 10−8, and 10−7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. We examined different vascular functions such as migration of ECs, adhesion of ECs to the extracellular matrix, tube formation, the morphology of rat aorta, as well as several signaling pathways involved in controlling endothelial function. Short-term in vitro exposure to DBP increased migration of ECs through G protein-coupled estrogen receptor, extracellular signal-regulated kinase 1/2, and nitric oxide (NO) signaling and decreased adhesion to gelatin. Long-term in vitro exposure to DBP transiently increased EC migration and had a bidirectional effect on EC adhesion to gelatin and tube formation. These effects were accompanied by a sustained increase in NO production and endothelial NO synthase (eNOS) and Akt activity. In vivo, exposure to DBP for 90 days decreased the aortic wall-to-lumen ratio and increased eNOS and Akt phosphorylation in ECs of rat aorta. This comparative investigation has shown that exposure to DBP may affect vascular function by altering EC migration, adhesion to gelatin, and tube formation after short- and long-term in vitro exposure and by decreasing the aortic wall-to-lumen ratio in vivo. The eNOS-NO and Akt signaling could be important in mediating the effects of DBP in long-term exposure scenarios. •Short-term exposure to DBP promotes migration of EA.hy926 cells via GPER and ERK1/2.•Long-term exposure to DBP increases migration and angiogenesis of EA.hy926 cells.•Long-term exposure to DBP activates eNOS-NO and Akt signaling in EA.hy926 cells.•Sub-chronic exposure to DBP decreases wall-to-lumen ratio of rat aorta.•Sub-chronic exposure to DBP activates eNOS and Akt in endothelial cells of rat aorta.
ISSN:0009-2797
1872-7786
1872-7786
DOI:10.1016/j.cbi.2024.111120