Mei Wang,Na Luo,Yanpeng Gao,Guiying Li,Taicheng An
Derivatives of polycyclic aromatic hydrocarbons (PAHs) pose significant threat to environment and human health due to their widespread and potential hazards. However, adverse effects and action mechanisms of PAH derivatives on human health have not been attempted yet. Herein, we chose pyrene and its derivatives (1-hydroxypyrene, 1-nitropyrene, and 1-methylpyrene) to investigate adverse effect mechanism to human lungs using in vitro and in vivo methods. Results showed that pyrene derivatives have higher lung health risks than original pyrene. They can activate AhR, subsequently affecting expression of downstream target genes CYP1A1 and CYP1B1. The binding energies of pyrene and its derivatives ranged from −16.07 to −27.25 kcal/mol by molecular dynamics simulations, implying that pyrene and its derivatives acted as agonists of AhR and increased adverse effects on lungs. Specifically, 1-nitropyrene exhibited stabler binding conformation and stronger AhR expression. In addition, sensitivity of pyrene and its derivatives to AhR activation was attributed to type and number of key amino acids in AhR, that is, pyrene (Leu293), 1-nitropyrene (Cys333, Met348, and Val381), 1-hydroxypyrene (Leu293 and Phe287), and 1-methylpyrene (Met348). In summary, we provide a universal approach for understanding action mechanisms of PAH derivatives on human health, and their adverse effects should be taken seriously.
Jin Chen,Yiwei Fang,Borui Sun,Ying Xu,Wanyi Chen,Kai zhao,Huiping Zhang
Polycyclic aromatic hydrocarbons (PAHs) are widespread pollutants from incomplete combustion of organic materials, linked to various health issues and pregnancy complications. This study explored the relationship between PAH metabolites and gestational hypertension. Urine samples from 118 normal pregnant women and 40 with gestational hypertension were analyzed. In vitro experiments using human trophoblast cells (HTR-8/SVneo) exposed to these metabolites assessed their effects on cellular metabolism. Comprehensive metabolomics analysis was performed using Tidymass and DRomics to integrate global and dose-response metabolomics data. Results showed higher levels of 1-hydroxypyrene (1-OHPYR) and 9-Hydroxyphenanthrene (9-OHPHE) linked to gestational hypertension, inhibiting trophoblast cell invasion and migration. Identified markers include Isobutyryl-L-carnitine, methyl-3-hydroxybutyric acid, threonine, and glutamic acid for 1-OHPYR, and phosphocreatine for 9-OHPHE. This study highlights the connection between PAH metabolites and gestational hypertension, suggesting potential biomarkers and mechanisms. Future research should confirm these findings and explore prevention and treatment strategies.
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