What question did this study set out to answer?

This study aims to clarify the molecular mechanisms of respiratory toxicity induced by TCEP.

July 3, 2026Journal of Biochemical and Molecular Toxicology0 citations

Tris(2‐Chloroethyl) Phosphate (TCEP) Induces Respiratory Toxicity Through Oxidative Stress and Multi‐Target Interactions: Evidence From Network Toxicology, Molecular Docking, and Experimental Validation

RGRuoyu GengXinjiang Medical University FYFei YeXinjiang Medical University QYQi YanCentral University of Finance and Economics

Key Points

This study aims to clarify the molecular mechanisms of respiratory toxicity induced by TCEP.
Utilized network toxicology and molecular docking to identify TCEP targets.
Conducted in vitro experiments on BEAS-2B cells to assess cytotoxicity and oxidative stress.
Verified binding affinities of TCEP targets using surface plasmon resonance.
TCEP exposure caused concentration-dependent cytotoxicity and oxidative stress in BEAS-2B cells.
MMP-9, MMP-2, and PTGS2 showed significant upregulation after TCEP treatment.
N-acetylcysteine pretreatment reduced the upregulation of targeted proteins, indicating dependence on oxidative stress.

Abstract

ABSTRACT Tris(2‐chloroethyl) phosphate (TCEP) is a ubiquitous organophosphorus flame retardant and an emerging environmental contaminant of concern; however, the specific molecular mechanisms underlying its respiratory toxicity remain poorly understood. This study aimed to systematically elucidate the respiratory toxicity mechanisms of TCEP using an integrated toxicological approach. An integrated strategy combining network toxicology, molecular docking, surface plasmon resonance (SPR), and in vitro experimental validation was adopted to systematically explore the respiratory toxicity mechanisms of TCEP in human bronchial epithelial BEAS‐2B cells. Network analysis revealed that potential TCEP targets were significantly enriched in pathways associated with inflammation and oxidative stress. Molecular docking identified MMP‐9, MMP‐2, and PTGS2 as core targets with strong binding affinities (−5.1 to −5.4 kcal/mol), and these results were further verified by SPR assays, which confirmed the direct binding of TCEP to these targets with micromolar affinities ( K D = 42.4–92.0 μM). In vitro experiments revealed that TCEP exposure triggered concentration‐dependent cytotoxicity and marked oxidative stress in BEAS‐2B cells, characterized by glutathione depletion, catalase inhibition, increased lipid peroxidation, and compensatory upregulation of superoxide dismutase. Additionally, TCEP significantly upregulated the protein expression levels of MMP‐9, MMP‐2, and PTGS2, while pretreatment with the ROS scavenger N‐acetylcysteine (NAC) significantly mitigated this upregulation, indicating that oxidative stress acts as a key upstream mediator responsible for the activation of these targets. These findings collectively demonstrate that TCEP impairs respiratory epithelial homeostasis via a synergistic multi‐target mechanism involving oxidative stress, inflammation, and tissue remodeling, which provides important theoretical support for environmental risk assessment and the development of targeted therapeutic interventions.

问 AI

Bookmark

View Full Paper