Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway

Wang, Jing; Meng, Xinyao; Feng, Chenzhao; Xiao, Jun; Zhao, Xiang; Xiong, Bo; Feng, Jiexiong

doi:10.1016/j.chemosphere.2021.130670

Cited by 23 publications

(9 citation statements)

References 86 publications

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“…The basis for the development of Hirschprung's disease is caused by failed neural crest cells migration into the distal colon occurring from the 5 th to 12 th week of the embryogenesis, resulting in a lack of innervation in this region. This finding has been confirmed by Wang and others (Wang et al, 2021), who demonstrated that exposure to benzophenone-3 induced a reduction in the number of enteric neurons and abnormal gastrointestinal physiology in zebrafish. In addition, benzophenone-3 has been shown to reduce the duration of pregnancy and increase the birth weight of newborns (Wolff et al, 2008;Tang et al, 2013;Philippat et al, 2014;Ferguson et al, 2018;Zhong et al, 2020).…”

Section: Exposure Routes Of the Human Body To Benzophenone-3supporting

confidence: 71%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, oxybenzone, or BP-3) is one of the most frequently used UV radiation absorbents, which are commonly referred to as sunscreen filters. Its widespread use in industrial applications provides protection against the photodegradation of a wide range of products but at the same time creates the risk of human exposure to benzophenone-3 unbeknownst to the individuals exposed. Topically applied benzophenone-3 penetrates individual skin layers, enters the bloodstream, and is excreted in the urine. In addition, benzophenone-3 easily crosses the placental barrier, which creates the risk of exposure to this substance in the prenatal period. Despite the widespread use and occurrence of benzophenone-3 in the human environment, little knowledge of the mechanisms underlying the effect of benzophenone-3 on the nervous system was available until recently. Only the most recent research, including studies by our group, has enabled the identification of new molecular mechanisms through which benzophenone-3 affects embryonic neuronal cells and the developing mammalian brain. Benzophenone-3 has been shown to induce neurotoxicity and apoptotic processes and inhibit autophagy in embryonic neuronal cells. Benzophenone-3 also alters expression and impairs function of receptors necessary for the proper development and function of the nervous system. The most worrying finding seems to be that benzophenone-3 contributes to an increased risk of developmental abnormalities and/or epigenetically based degeneration of neuronal cells by changing the epigenetic status of neuronal cells.

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Section: Exposure Routes Of the Human Body To Benzophenone-3supporting

confidence: 71%

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Wnuk

Kajta

2021

Acta Biochim Pol

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“…The study found that inhibition of the MAPK pathway leads to abnormal intestinal neurodevelopment in zebrafish. Intestinal neurodevelopment is an important process of embryonic development [ 36 ]. Our data support embryotoxicity by inhibiting differentiation or cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology

Liu

Yang

Yang³

et al. 2023

Toxins

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Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

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“…Environmental risk factors for IBD include smoking, antibiotic use in childhood, low vitamin D levels, and diet ( 23 ). In terms of HSCR, benzophenone-3, lovastatin, and mycophenolic have been reported to cause the delayed development of the enteric nervous system and HSCR-like phenotypes ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn’s disease

Wang

Xiao

et al. 2022

Front. Immunol.

Self Cite

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BackgroundAlthough increasing evidence has supported that Hirschsprung disease (HSCR) is the risk factor for children developing Crohn’s disease (CD), the common mechanism of its co-occurrence remains unknown. The purpose of this study is to further explore the underlying mechanism and biomarkers for the co-occurrence of HSCR and CD.MethodsThe Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles for CD (GSE95095) and HSCR (GSE98502). Following the identification of the shared differentially expressed genes (DEGs) of CD and HSCR, functional annotation, protein–protein interaction (PPI) network creation, and module assembly were performed to discover hub genes. RT-qPCR was performed to validate the expression of the hub genes in HSCR samples. The receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the hub genes as biomarkers in predicting CD in both the training dataset and test dataset.ResultsA total of 103 common DEGs (50 downregulated genes and 53 upregulated genes) were chosen for further investigation. The importance of chemokines and cytokines in these two disorders is highlighted by functional analysis. MCODE plug identified three important modules, which functionally enriched the immune system process. Finally, nine hub genes were identified using cytoHubba, including IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1. The nine hub genes were mainly enriched in immune- and inflammation-related pathways. External data profiles and RT-qPCR confirmed the expression of the nine hub genes in HSCR and CD. ROC analysis revealed that the nine hub genes had a strong diagnostic value.ConclusionOur study reveals the common pathogenesis of HSCR and CD. These hub genes and diagnostic models may provide novel insight for the diagnosis and treatment of HSCR complicated with CD.

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Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway

Cited by 23 publications

References 86 publications

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology

Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn’s disease

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