ENVIRONMENT INTERNATIONAL
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2025
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IF 9.7
Jianrong Han,Changqian Liu,Zhiyuan Chen,Fengkai Ruan,Fanzheng Xue,Lingxiao Ye,Yi Yu,Zhenghong Zuo,Chengyong He
Metabolic-associated fatty liver disease (MAFLD), linked to lipid dysregulation, poses global health risks. 2,2′,3,4,4′,5′-hexachlorobiphenyl (PCB138) is a persistent organic pollutant that poses potential threats to liver health due to its environmental persistence and bioaccumulation. Theabrown (TB), a natural compound extracted from black tea, exhibits lipid-lowering and antioxidant properties, but its protective effects on PCB138-induced liver injury have not been thoroughly investigated. Following a biphasic experimental design, juvenile male C57BL/6J mice were subjected to chronic PCB138 exposure (100 μg/kg, oral gavage every other day) for 48 weeks, with subsequent administration of TB (225 mg/kg/day) for an 8-week recovery duration. Long-term PCB138 exposure resulted in elevated liver/body weight ratio, hepatic triglyceride/cholesterol accumulation, and histopathological lipidosis, confirming MAFLD progression. Mechanistically, chronic oral exposure to PCB138 induced multi-organ dysregulation, characterized by: (i) intestinal barrier disruption, (ii) gut microbiota dysbiosis, (iii) disruption of the gut-liver bile acid axis accompanied by hepatic accumulation of lithocholic acid (LCA), taurolithocholic acid (TLCA), taurodeoxycholic acid (TDCA), and glycodeoxycholic acid (GDCA), and (iv) upregulated hepatic fatty acid synthase (FASN) expression, thereby accelerating de novo lipogenesis. TB administration for another 8 weeks attenuated these MAFLD manifestations, evidenced by mitigated hepatic lipidosis, repaired intestinal defenses, microbiota normalization, and bile acids rebalance. Using alpha mouse liver 12 (AML12) cells, we demonstrated that GDCA activated sterol regulatory element-binding protein 1 (SREBP1) expression, promoting lipogenesis. This study establishes long-term environmental PCB138 exposure as a driver of MAFLD via gut-liver axis activating lipogenic pathways and microbial-metabolic crosstalk. TB emerges as a potential protective agent by targeting bile acids-mediated SREBP1/FASN signaling, offering insights into environmental pollutant toxicity mitigation and MAFLD management.
研究领域:
环境毒理学
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肝病学
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营养科学
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微生物学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
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IF 6.7
Xiaoyan Ding,Yuting Zhong,Zhiyuan Chen,Chao Shen,Moye Ren,Lin Zhong,Changshun Han,Changqian Liu,Zitong Huang,Junwei Chen,Wei Zeng,Chengyong He,Zhenghong Zuo
2,2′,3,4,4′,5′-Hexachlorobiphenyl (PCB138) is a persistent organic pollutant with potential intestinal toxicity. Theabrownin (TB) can improve intestinal injury, but its protective effect against PCB138 remains unclear. This study found that 48-week PCB138 exposure induced ileal damage, inflammation, oxidative stress, and necroptosis in mice, which were mitigated by TB intervention. TB alleviated PCB138-induced intestinal damage by suppressing oxidative-stress-mediated intestinal epithelial cell necroptosis. Mechanistically, both TB and N-acetylcysteine (NAC) suppressed PCB138-triggered ROS and subsequent RIPK1/RIPK3/MLKL phosphorylation. The additive effect of NAC combined with necrostatin-1 confirmed ROS as the upstream trigger and RIPK1 as the downstream executor. TB acts similar to NAC, establishing that it prevents necroptosis by scavenging upstream ROS. This study revealed a new mechanism of PCB138-induced intestinal toxicity and identified TB as a potential protective agent against environmentally pollutant-triggered intestinal inflammation.
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DOI
PubMed
高影响因子
Journal of Environmental Sciences
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2026
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IF 6.5
Jinpeng Ruan,Pengtao Chen,Yixi Zhou,Zhiyuan Chen,Rongrong He,Min Xiao,Mingyue Chen,Chen Tang,Chao Shen,Jiali Cai,Chengyong He,Xiaoming Jiang,Zhenghong Zuo
Neonatal exposure to environmentally relevant levels of PCB138 induces a PCOS-like phenotype in adult mice. • PCB138 acts as an Aryl Hydrocarbon Receptor (AhR) agonist to activate the AhR signaling pathway in ovarian granulosa cells. • AhR activation by PCB138 disrupts steroidogenesis by upregulating the expression of key enzymes StAR and CYP11A1. • Granulosa cell-specific Ahr knockout or pharmacological antagonism effectively rescues PCB138-induced endocrine and ovarian dysfunction. Polycystic ovary syndrome (PCOS), a highly prevalent reproductive disorder affecting reproductive-age women, has been increasingly associated with exposure to environmental pollutants. Polychlorinated biphenyls (PCBs), recognized as environmentally persistent organic pollutants, have been detected in PCOS patients, yet their mechanistic contribution to the syndrome remains to be elucidated. In this study, the reproductive effects of PCB138, a congener frequently detected in the environment and human tissues, were assessed in female mice using environmentally relevant exposure levels. PCB138 exposure led to irregular estrous cycles, abnormal follicular development, and dysregulated steroidogenesis (high testosterone, low estradiol). Furthermore, we found that PCB138 exposure induced aryl hydrocarbon receptor (AhR) activation, leading to dysregulated steroidogenesis as demonstrated by both in vivo and in vitro experiments. AhR antagonist CH223191 treatment attenuated PCB138-induced abnormal steroidogenesis in human granulosa cells. Ovarian granulosa cell-specific Ahr -knockout mitigated PCB138-induced alterations in the estrus cycle, ovarian steroidogenesis, and follicle development. In summary, this study demonstrates that neonatal exposure to environmental levels of PCB138 induces hyperandrogenism and ovulatory dysfunction, leading to PCOS features through AhR activation. Investigation of AhR as a key regulator of PCB-induced PCOS uncovers new mechanistic insight and suggests potential therapeutic strategies to improve female reproduction. Download: Download high-res image (312KB) Download: Download full-size image
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DOI
高影响因子
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