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Turkish Journal of Medical Sciences

Author ORCID Identifier

ELİF KELEŞ: 0000-0001-8103-797X

LATİFE ARAL: 0000-0002-7300-1624

ZÜBEYİR ELMAZOĞLU: 0000-0003-4527-8834

HASAN KAZAN: 0000-0001-7936-8606

ELİF ABBASOĞLU TOPA: 0000-0001-5140-1451

MEHMET ERGÜN: 0000-0001-9696-0433

HAYRUNNİSA BOLAY: 0000-0002-3357-7733

DOI

10.55730/1300-0144.5889

Abstract

Background/aim: Phthalates are the materials used for plasticizing polyvinyl chloride. Di-(2-Ethylhexyl) phthalate (DEHP) is one of the most frequently used phthalates in a wide range of applications, including medical equipment such as endotracheal and feeding tubes, intravenous catheters, central lines, extracorporeal membrane oxygenation sets, total parenteral nutrition bags, blood product sets, and intravenous pump lines, respiratory sets in neonatal intensive care units. Studies have shown that phthalates, including DEHP, can cross the placenta and blood-brain barrier, possibly leading to neurodevelopmental impairments in vitro and in vivo. However, the molecular mechanisms affected by phthalate exposure have not been explored in depth. Our study aims to illuminate the effects of DEHP on neuroinflammation at the molecular level using neonatal microglial cells as the model.Materials and methods: Mouse BV-2 neonatal microglia cells were exposed to DEHP under controlled conditions. We assessed cellular toxicity via a cell viability assay and used specific markers to evaluate apoptosis/necrosis, cellular iron content, reactive oxygen species (ROS), and organelle integrity. Proinflammatory proteins were quantified using enzyme-linked immunosorbent assay (ELISA), while ferroptosis was assessed using a ferroptosis blocker, and affected gene expressions were figured out using real-time polymerase chain reaction (RT-PCR).Results: Our results figured out that high concentrations of DEHP exposure increased toxicity via increased levels of ROS and inflammation. Elevated ROS was detected to increase the tendency for mitochondrial-lysosomal disruption, bringing about apoptosis or necrosis. Moreover, iron homeostasis was dysregulated by DEHP, which putatively triggered ferroptosis in a dose-dependent manner.Conclusion: This study indicates that neonatal exposure to DEHP may be linked to neurodevelopmental impairments via inflammation-related cell death and ferroptosis. The prevalence of DEHP in neonatal intensive care unit (NICU) medical devices raises concerns about potential neurodevelopmental deficits, including disorders like autism and mental retardation. These findings highlight the urgency of addressing DEHP exposure in neonatal care.

Keywords

DEHP, ferroptosis, inflammation, microglia, Phthalate

First Page

1102

Last Page

1115

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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