Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Chen, Honghong; Zheng, Yan; Yang, Xuanjun; Chen, Fangyi; Chen, Jiaying; Tang, Liang; Zhong, Hanbing; Magnuson, Jason T.; Chen, Kewei; Xu, Elvis Genbo

doi:10.1021/acs.est.1c08875

Cited by 41 publications

(14 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 It has been reported that exogenous compounds, such as tetrachlorodibenzo-p-dioxin (TCDD), stimulated the expression of pro-inflammatory factor iL-1β by activating AhRs in cerebral endothelial cells, which in turn induces BBB damage and development of various neurological diseases. 36 Recently, Chen et al 37 demonstrated that perfluorooctane sulfonamide (PFOSA) induced cardiotoxicity via AhR activation in zebrafish. Although PFPiAs might bind with various proteins, 22 it remains unclear whether they have the potential to activate AhR to induce brain inflammation and neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Novel Insight into the Mechanisms of Neurotoxicity Induced by 6:6 PFPiA through Disturbing the Gut–Brain Axis

Zhao

Dong

Jia

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

As alternatives to traditional per-and polyfluoroalkyl substances, perfluoroalkyl phosphonic acids (PFPiAs) are frequently detected in aquatic environments, but the neurotoxic effects and underlying mechanisms remain unclear. In this study, male zebrafish were exposed to 6:6 PFPiA (1 and 10 nM) for 28 days, which exhibited anxiety-like symptoms. Gut microbiome results indicated that 6:6 PFPiA significantly increased the abundance of Gram-negative bacteria, leading to enhanced levels of lipopolysaccharide (LPS) and inflammation in the gut. The LPS was delivered to the brain through the gut− brain axis (GBA), damaged the blood−brain barrier (BBB), stimulated neuroinflammation, and caused apoptosis as well as neural injury in the brain. This mechanism was verified by the fact that antibiotics reduced the LPS levels in the gut and brain, accompanied by reduced inflammatory responses and anxiety-like behavior. The BBB damage also resulted in the enhanced accumulation of 6:6 PFPiA in the brain, where it might bind strongly with and activate aryl hydrocarbon receptor (AhR) to induce brain inflammation directly. Additionally, as the fish received treatment with an inhibitor of AhR, the inflammation response and anxiety-like behavior decreased distinctly. This study sheds light on the new mechanisms of neurotoxicity-induced 6:6 PFPiA due to the interruption on GBA.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Insight into the Mechanisms of Neurotoxicity Induced by 6:6 PFPiA through Disturbing the Gut–Brain Axis

Zhao

Dong

Jia

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…The ubiquity of PFASs in the environment may threaten the health of aquatic organisms due to the strong bioenrichment and potential toxicity at environmental concentrations. − Previous studies have confirmed that the immune system is a sensitive target to PFASs . Perfluorooctanesulfonate (PFOS) and its alternatives, chlorinated polyfluorinated ether sulfonate and sodium p-perfluorous nonenoxybenzene sulfonate, disrupted an antioxidant response and induced anti-inflammatory effects in exposed zebrafish larvae .…”

Section: Introductionmentioning

confidence: 99%

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.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…The heart is the first functional organ of development in vertebrates such as fish, providing nutrients and oxygen to the brain and systemic systems (Chen et al, 2022). Therefore cardiotoxicity induced by environmental pollutants may disrupt blood circulation and threaten the development of other organs or even life (Ma, Huang, Jiang, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress contributes to flumioxazin‐induced cardiotoxicity in zebrafish embryos

Ma,

Jiang,

Huang

et al. 2023

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Flumioxazin is a widely applicated herbicide in the control of aquatic plants. Current evidence suggested that flumioxazin could induce cardiac defects (ventricular septal defects) in vertebrates, but the underlining mechanisms remain unclear. Because of the inhibitory effect of flumioxazin on polyphenol oxidase (PPO), the assumption is made that flumioxazin‐induced cardiotoxicity is caused by oxidative stress. The results show that flumioxazin induced cardiac malformations and abnormal gene expression associated with cardiac development. Cardiac malformations include pericardium edema, cardiac linearization, elongated heart, cardiomegaly, cardiac wall hypocellularity, myocardial cell atrophy into granular, and a significant gap between the myocardial intima and the adventitia. An increase in oxidative stress and apoptosis was observed in the cardiac region of zebrafish after exposure to flumioxazin. Antioxidant astaxanthin reversed the cardiac malformations, excessive ROS production and expression of genes for cardiac developmental and apoptosis regulation induced by flumioxazin. In addition, flumioxazin also activated AHR signaling pathway genes (ahr2, cyp1a1, and cyp1b1) and increased porphyrins concentration. In conclusion, the results suggest that excessive ROS production, which could be mediated through AHR, led to apoptosis, contributing to the cardiotoxicity of flumioxazin in zebrafish embryos.

show abstract

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Cited by 41 publications

References 53 publications

Novel Insight into the Mechanisms of Neurotoxicity Induced by 6:6 PFPiA through Disturbing the Gut–Brain Axis

Novel Insight into the Mechanisms of Neurotoxicity Induced by 6:6 PFPiA through Disturbing the Gut–Brain Axis

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

Oxidative stress contributes to flumioxazin‐induced cardiotoxicity in zebrafish embryos

Contact Info

Product

Resources

About