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AhR-mediated CYP1A1 and ROS overexpression are involved in hepatotoxicity of decabromodiphenyl ether (BDE-209).
- Source :
-
Toxicology Letters . Nov2021, Vol. 352, p26-33. 8p. - Publication Year :
- 2021
-
Abstract
- • Nrf2 negatively regulates BDE-209-induced oxidative stress. • BDE-209 triggers mitochondrial dysfunction, disordered calcium homeostasis, and DNA damage. • The toxicity mechanism of BDE-209 may be related to the dysfunction of organelles and Nrf2 signaling pathways. Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants. They are constantly detected in terrestrial, ocean, and atmospheric systems, and it is of particular concern that these fat-soluble xenobiotics may have a negative impact on human health. This study aimed to evaluate the toxic effect and underlying mechanism of decabromodiphenyl ether (BDE-209) on human liver in a HepG2 cell model. The results showed that BDE-209 significantly induced HepG2 cells apoptosis, increased intracellular reactive oxygen species (ROS), disturbed [Ca 2+] homeostasis and mitochondrial membrane potential (MMP), and caused nuclear shrinkage and DNA double-strand breaks. BDE-209 also significantly decreased the activities of antioxidant parameters, superoxide dismutase (SOD), total antioxygenic capacity (T-AOC), glutathione (GSH), and total glutathione (T-GSH). The up-regulation of the Aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 (CYP1A1) signaling pathway indicates that after long-term and high-dose exposure, BDE-209 may be a liver carcinogen. Interestingly, HepG2 cells attempt to metabolize BDE-209 through the Nrf2-mediated antioxidant pathway. These findings help elucidate the mechanisms of BDE-209-induced hepatotoxicity in humans. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03784274
- Volume :
- 352
- Database :
- Academic Search Index
- Journal :
- Toxicology Letters
- Publication Type :
- Academic Journal
- Accession number :
- 153120851
- Full Text :
- https://doi.org/10.1016/j.toxlet.2021.09.008