Aug 2026· Journal of Agricultural and Food Chemistry· 0 citations· 48 references
TL;DR
BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.
Abstract
2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is a persistent food-chain pollutant targeting the liver, whose genotoxic potential remains poorly understood. Here we investigated BDE-47-triggered DNA damage using HepG2 cells and C3H/He mice. BDE-47 exposure markedly elevated DNA damage-related γ-H2AX foci in mouse liver. Cellular tests further validated BDE-47-induced DNA damage, manifested as elevated γ-H2AX foci, a higher comet tail DNA percentage, and a longer tail length. Mechanistically, BDE-47 activated the aryl hydrocarbon receptor (AHR) and raised hepatic reactive oxygen species (ROS) and malondialdehyde levels. In cellular assays, antioxidants alleviated DNA damage, whereas AHR inhibitors suppressed ROS overproduction. BDE-47 also upregulated hepatic CYP1A1/2, whose expression positively correlated with the severity of hepatic DNA injury in mice. In conclusion, BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.
It is suggested that EHDPP may enhance protein expression of hepatic Cyp1a1, Cyp2e1, AhR and PXR and induce liver damage and DNA/chromosome damage in mice; Cyp1a1 might be a major activating enzyme.
Zhao Zhou, Hongbin Gao, Shunda Zhu et al.· Toxics· 0 citations
The findings reveal close associations between DCHP exposure and testicular injury, proposing a working model involving oxidative stress and inflammation; however, further functional studies are required to establish definitive causal relationships.
Qianni Li, Yang Yang, Danni Jiang et al.· Reproductive Toxicology· 0 citations
Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer and a classified Group 2B carcinogen, is associated with increased colorectal cancer (CRC) incidence, but its causal role and mechanisms are unclear. We investigated DEHP toxicity in human colonic epithelial cells (NCM460) using an integrated multi-omics approach. Phenotypic assays showed that low-dose (200 μM) exposure markedly inhibited cell migration by 32% independent of cytotoxicity within 48 h. Transcriptomics revealed a biphasic stress response: an early disruption of cholesterol metabolism and ABC transporters, followed by activation of pro-oncogenic pathways. Metabolomics confirmed concurrent redox imbalance and lipid/steroid dysregulation. Integrated analysis identified ABCA1, ABCG1, and SREBF1 as central regulatory nodes linking metabolic dysfunction to inflammatory and oncogenic pathways. The downregulation of ABCA1 and ABCG1 was validated at the mRNA level, a finding corroborated by their significant underexpression in clinical CRC tumors (TCGA database). Tumor tissues exhibited a 0.54-fold decrease in ABCA1 and a 0.47-fold decrease in ABCG1 compared to normal controls (p < 0.0001, n = 286). Moreover, ABCA1 knockdown phenocopied the inhibitory effect of DEHP on cell migration. In conclusion, these findings suggest that short-term DEHP exposure may disrupt intestinal epithelial homeostasis through a mechanism involving cholesterol transport impairment (SREBF1/ABCA1/ABCG1 axis), representing an early event in DEHP-associated colorectal pathogenesis.
Xinrui Zhou, Jiayi Diao, Jiamin Lu et al.· Ecotoxicology and Environmen...· 0 citations
Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and environmental contaminant. DEHP exposure has been linked to neurotoxicity in Alzheimer's disease (AD), yet the underlying mechanisms remain unclear. Here we found that DEHP exacerbated amyloid-beta (Aβ)-induced toxicity in transgenic AD Caenorhabditis elegans (C. elegans) models. Meanwhile the accumulation of SQST-1 was increased, indicating that the autophagic flux was impaired. Consistently, Aβ deposition was elevated in DEHP-treated AD C. elegans. Further investigation revealed that DEHP treatment resulted in lysosomal dysfunction accompanied by a significant decrease in lysosome number. The expression of hlh-30, a key transcription factor involved in lysosomal biogenesis, as well as its downstream lysosome-related genes, including cup-5, vha-17, and lmp-1, was reduced by DEHP. Moreover, hlh-30 RNAi abolished the exacerbation of Aβ toxicity by DEHP, indicating that the modulation of hlh-30 was a critical mechanism underlying the effects of DEHP. Additionally, DEHP aggravated oxidative stress in AD C. elegans, while the antioxidant N-acetylcysteine alleviated lysosomal impairment and reduced Aβ deposition, suggesting that the elevated oxidative stress was a key contributor to DEHP-induced lysosomal dysfunction and autophagy impairment. These findings highlight lysosomal impairment as a key mechanism contributing to DEHP-exacerbated toxicity in AD models, and suggest the possibility of using antioxidants to prevent DEHP-induced toxicity.
Fan Yang, Yan Zhao· Food and Chemical Toxicology· 0 citations
As a persistent organic pollutant (POP), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) can accumulate through the food chain and enter the human body. Most existing studies have focused on short-term toxicity, with insufficient understanding of its chronic toxicity. In this study, a 6-month chronic exposure model was established in C3H/He mice via intragastric gavage. Hematological analysis and biochemistry tests were conducted, and organ coefficients along with histopathological changes were analyzed. Additionally, liver ultrasound elastography was assessed. The results showed that BDE-47 could significantly reduce renal index, serum levels of albumin (ALB), triglycerides (TG), and urea (UREA), increase uric acid (UA) levels, cause a dose-dependent decrease in liver elasticity, and lead to hepatic steatosis, atrophy of seminal vesicle epithelium, shedding of spermatogenic cells, and infiltration of splenic macrophages. Collectively, this study has confirmed that BDE-47 has significant chronic toxicity to mammals, providing a new basis for subsequent toxicological research and safety risk evaluation.
Wei Deng, Xiaojing Liu, Xiaobing Wu et al.· Food and Chemical Toxicology· 0 citations