Insights into the spatiotemporal occurrence and mixture risk assessment of household and personal care products in the waters from rivers to Laizhou Bay, southern Bohai Sea
“…The average total concentration of the five OPEs (TCEP, TCPP, TDCPP, TNBP, and TPHP) in the surface water of the Bohai Sea decreased from 127 ng L −1 in May 2019 ( Qi et al, 2022 ) to 29 ng L −1 in April 2020 ( Zheng et al, 2022 ) with a reduced rate of 77%, similar to the results of our study. However, COVID-19 pandemic led to the significant increase in the concentrations of antibiotics (erythromycin, norfloxacin, and ciprofloxacin), preservatives (para-hydroxybenzoic acid and methylparaben), and endocrine-disrupting chemicals (bisphenol-A) in the LZB water ( Lu, 2022 ; Lu et al, 2022 ). Fig.…”
“…The average total concentration of the five OPEs (TCEP, TCPP, TDCPP, TNBP, and TPHP) in the surface water of the Bohai Sea decreased from 127 ng L −1 in May 2019 ( Qi et al, 2022 ) to 29 ng L −1 in April 2020 ( Zheng et al, 2022 ) with a reduced rate of 77%, similar to the results of our study. However, COVID-19 pandemic led to the significant increase in the concentrations of antibiotics (erythromycin, norfloxacin, and ciprofloxacin), preservatives (para-hydroxybenzoic acid and methylparaben), and endocrine-disrupting chemicals (bisphenol-A) in the LZB water ( Lu, 2022 ; Lu et al, 2022 ). Fig.…”
“…The TCS content in commercial products may reach as high as 17 mmol/L (0.5%) [ 5 ]. Although the use of TCS in antiseptic soaps was phased out in the United States in 2016 by FDA, it is still widely used in a wide range of personal care and health care products (such as toothpaste, mouthwash, shampoo, deodorant and cosmetics) in many countries [ 60 – 63 ]. The wide use and chemical persistence of TCS have also led to substantial accumulation in the environment, thus causing severe pollution problems [ 64 , 65 ].…”
Background
Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.
Methods
C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mouse livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the molecular and cellular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red staining. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.
Results
We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control group profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis.
Conclusions
TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mouse livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.
“…This increase in the concentration of contaminants was attributed to the usage of pharmaceuticals for COVID-19 prevention. 174 Before the COVID-19 outbreak, many studies had already been carried out globally on environmental contamination by PPCPs. Fig.…”
Section: Covid-19 and Environmental Contamination By Emerging Contami...mentioning
confidence: 99%
“…This increase in the concentration of contaminants was attributed to the usage of pharmaceuticals for COVID-19 prevention. 174…”
Section: Partitioning Between Water and Sediment And Bioaccumulation ...mentioning
Over the last few decades, the occurrence of pharmaceuticals and personal care products (PPCPs) in aquatic environments has generated increasing public concern. In this review, data on the presence of...
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