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

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier
      Original Publication: Amsterdam, Elsevier.
    • Subject Terms:
      Dibutyl Phthalate*/toxicity ; Cell Movement*/drug effects ; Cell Adhesion*/drug effects ; Endothelial Cells*/drug effects ; Endothelial Cells*/metabolism; Animals ; Humans ; Rats ; Male ; Nitric Oxide Synthase Type III/metabolism ; Signal Transduction/drug effects ; Nitric Oxide/metabolism ; Aorta/drug effects ; Cell Line ; Proto-Oncogene Proteins c-akt/metabolism ; Rats, Sprague-Dawley ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism
    • Abstract:
      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.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Akt; Angiogenesis; Cell migration; Dibutyl phthalate; Endothelial cells; Nitric oxide
    • Accession Number:
      2286E5R2KE (Dibutyl Phthalate)
      EC 1.14.13.39 (Nitric Oxide Synthase Type III)
      31C4KY9ESH (Nitric Oxide)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
    • Publication Date:
      Date Created: 20240629 Date Completed: 20240731 Latest Revision: 20240731
    • Publication Date:
      20240801
    • Accession Number:
      10.1016/j.cbi.2024.111120
    • Accession Number:
      38944327