Perfluorooctanoic acid-induced immunotoxicity via NF-kappa B pathway in zebrafish (Danio rerio) kidney

Zhang, Hangjun; Shen, Lilai; Fang, Wendi; Zhang, Xiaofang; Zhong, Yuchi

doi:10.1016/j.fsi.2021.03.004

Cited by 33 publications

(16 citation statements)

References 38 publications

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“…However, under PFAS exposures, both innate and adaptive responses in zebrafish were impaired, which made zebrafish larvae vulnerable to Gram-negative Vibrio parahaemolyticus, even at low concentrations of 0.1 μg/L PFNA. Previous studies on PFOA and PFOS also confirmed a disturbance of cytokines, immunoglobulin, and kidney immune cell number following exposure. , The widespread detection of PFAS compounds increases the concern of early-life-stage fish and susceptibility to infection and disease due to a reduced immune response at concentrations detected in aquatic systems. , …”

Section: Discussionmentioning

confidence: 85%

“…51 Several PFASs have been reported to selectively bind the TLR family directly. 45,53−55 PFOA causes disturbances in the expression of cytokines and secretion of immunoglobulin levels by affecting the TLR/MyD88/NF-κB pathway in zebrafish 45 and induces an inflammatory response in the hippocampus of obese mice through the induction of TLR4 and IL-6 expression. 56 These findings suggest that PFASs can modulate the TLR pathway, although the specific cellular and molecular mechanisms have not been confirmed.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies on PFOA and PFOS also confirmed a disturbance of cytokines, immunoglobulin, and kidney immune cell number following exposure. 15,45 The widespread detection of PFAS compounds increases the concern of early-life-stage fish and susceptibility to infection and disease due to a reduced immune response at concentrations detected in aquatic systems. 46,47 Carbon chain length is an important factor in the bioaccumulation and bioenrichment of PFASs, which are directly related to health disturbance.…”

Section: Discussionmentioning

confidence: 99%

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Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

Tang

Zheng

Zhang

et al. 2023

Environ. Sci. Technol.

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Previous studies have reported the immunotoxicity of per-and polyfluoroalkyl substances (PFASs), but it remains a significant challenge to assess over 10,000 distinct PFASs registered in the distributed structure-searchable toxicity (DSSTox) database. We aim to reveal the mechanisms of immunotoxicity of different PFASs and hypothesize that PFAS immunotoxicity is dependent on the carbon chain length. Perfluorobutanesulfonic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) representing different carbon chain lengths (4−9) at environmentally relevant levels strongly reduced the host's antibacterial ability during the zebrafish's early-life stage. Innate and adaptive immunities were both suppressed after PFAS exposures, exhibiting a significant induction of macrophages and neutrophils and expression of immune-related genes and indicators. Interestingly, the PFAS-induced immunotoxic responses were positively correlated to the carbon chain length. Moreover, PFASs activated downstream genes of the toll-like receptor (TLR), uncovering a seminal role of TLR in PFAS immunomodulatory effects. Myeloid differentiation factor 88 (MyD88) morpholino knock-down experiments and MyD88 inhibitors alleviated the immunotoxicity of PFASs. Overall, the comparative results demonstrate differences in the immunotoxic responses of PFASs due to carbon chain length in zebrafish, providing new insights into the prediction and classification of PFASs mode of toxic action based on carbon chain length.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

Tang

Zheng

Zhang

et al. 2023

Environ. Sci. Technol.

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“…The fish immune system is very important to the host’s defense, comprehending an important barrier for the body to resist external stimuli such as pathogenic microbial infections ( 78 ). Meanwhile, it is also affected by various environmental pollutants, including drugs ( 79 , 80 ). We showed that in the early stage of acute exposure to a high concentration of Del, the transcriptome of channel catfish trunk kidney was enriched for many immune-related DEGs, including toll-like receptor, chemokine family, and IL-1β.…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq and 16S rRNA Analysis Revealed the Effect of Deltamethrin on Channel Catfish in the Early Stage of Acute Exposure

Yang¹,

Zhu²,

Huang³

et al. 2022

Front. Immunol.

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Deltamethrin (Del) is a widely used pyrethroid insecticide and a dangerous material that has brought serious problems to the healthy breeding of aquatic animals. However, the toxicological mechanisms of Del on channel catfish remain unclear. In the present study, we exposed channel catfish to 0, 0.5, and 5 μg/L Del for 6 h, and analyzed the changes in histopathology, trunk kidney transcriptome, and intestinal microbiota composition. The pathological analyses showed that a high concentration of Del damaged the intestine and trunk kidney of channel catfish in the early stage. The transcriptome analysis detected 32 and 1837 differentially expressed genes (DEGs) in channel catfish trunk kidneys after exposure to 0.5 and 5 μg/L Del, respectively. Moreover, the KEGG pathway and GO enrichment analyses showed that the apoptosis signaling pathway was significantly enriched, and apoptosis-related DEGs, including cathepsin L, p53, Bax, and caspase-3, were also detected. These results suggested that apoptosis occurs in the trunk kidney of channel catfish in the early stage of acute exposure to Del. We also detected some DEGs and signaling pathways related to immunity and drug metabolism, indicating that early exposure to Del can lead to immunotoxicity and metabolic disorder of channel catfish, which increases the risk of pathogenic infections and energy metabolism disorders. Additionally, 16S rRNA gene sequencing showed that the composition of the intestinal microbiome significantly changed in channel catfish treated with Del. At the phylum level, the abundance of Firmicutes, Fusobacteria, and Actinobacteria significantly decreased in the early stage of Del exposure. At the genus level, the abundance of Romboutsia, Lactobacillus, and Cetobacterium decreased after Del exposure. Overall, early exposure to Del can lead to tissue damage, metabolic disorder, immunotoxicity, and apoptosis in channel catfish, and affect the composition of its intestinal microbiota. Herein, we clarified the toxic effects of Del on channel catfish in the early stage of exposure and explored why fish under Del stress are more vulnerable to microbial infections and slow growth.

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“…Another research study in which immunotoxicity induced by perfluorooctanoic acid in zebrafish kidney showed that PFOA can regulate the transcription of cytokines by affecting the transcription factors of the NF-κB family members. PFOA may initially attack toll-like receptor (TLR) and affect MyD88 and NF- κ B pathways to regulate cytokine transcription and induce zebrafish immune system imbalance ( Zhang et al, 2021 ). After acute oral exposure to PFOA, epigenetic changes (including DNA methylation and HDAC expression) in mouse kidney tissue and kidney promote the expression of early markers of fibroblast activation ( Rashid et al, 2020 ).…”

Section: Perfluorooctanoic Acid (Pfoa) and Renal Tumorsmentioning

confidence: 99%

Perfluorooctanoic acid (PFOA) exposure in relation to the kidneys: A review of current available literature

et al. 2023

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Perfluorooctanoic acid is an artificial and non-degradable chemical. It is widely used due to its stable nature. It can enter the human body through food, drinking water, inhalation of household dust and contact with products containing perfluorooctanoic acid. It accumulates in the human body, causing potential harmful effects on human health. Based on the biodegradability and bioaccumulation of perfluorooctanoic acid in the human body, there are increasing concerns about the adverse effects of perfluorooctanoic acid exposure on kidneys. Research shows that kidney is the main accumulation organ of Perfluorooctanoic acid, and Perfluorooctanoic acid can cause nephrotoxicity and produce adverse effects on kidney function, but the exact mechanism is still unknown. In this review, we summarize the relationship between Perfluorooctanoic acid exposure and kidney health, evaluate risks more clearly, and provide a theoretical basis for subsequent research.

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Perfluorooctanoic acid-induced immunotoxicity via NF-kappa B pathway in zebrafish (Danio rerio) kidney

Cited by 33 publications

References 38 publications

Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

RNA-Seq and 16S rRNA Analysis Revealed the Effect of Deltamethrin on Channel Catfish in the Early Stage of Acute Exposure

Perfluorooctanoic acid (PFOA) exposure in relation to the kidneys: A review of current available literature

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