PREDICTION OF LIPOTOXICITY OF POLYFLUOROALKYL PHOSPHATE DIESTERS TO ZEBRAFISH BASED ON 3D-QSAR

CHEN Pengyu; HU Yuxi; CHEN Geng; ZHAO Na; DOU Zhichao

doi:10.13205/j.hjgc.202402029

Volume 42 Issue 2

Feb. 2024

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CHEN Pengyu, HU Yuxi, CHEN Geng, ZHAO Na, DOU Zhichao. PREDICTION OF LIPOTOXICITY OF POLYFLUOROALKYL PHOSPHATE DIESTERS TO ZEBRAFISH BASED ON 3D-QSAR[J]. ENVIRONMENTAL ENGINEERING , 2024, 42(2): 247-254. doi: 10.13205/j.hjgc.202402029

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CHEN Pengyu, HU Yuxi, CHEN Geng, ZHAO Na, DOU Zhichao. PREDICTION OF LIPOTOXICITY OF POLYFLUOROALKYL PHOSPHATE DIESTERS TO ZEBRAFISH BASED ON 3D-QSAR[J]. ENVIRONMENTAL ENGINEERING , 2024, 42(2): 247-254. doi: 10.13205/j.hjgc.202402029

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PREDICTION OF LIPOTOXICITY OF POLYFLUOROALKYL PHOSPHATE DIESTERS TO ZEBRAFISH BASED ON 3D-QSAR

doi: 10.13205/j.hjgc.202402029

CHEN Pengyu^{1,2
,
,},
HU Yuxi¹,
CHEN Geng³,
ZHAO Na¹,
DOU Zhichao¹

1. Jiangsu Province Engineering Research Center for Marine Bio-resources Sustainable Utilization, College of Oceanography, Hohai University, Nanjing 210024, China;
2. Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, Hohai University, Nanjing 210024, China;
3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Received Date: 2023-04-18
Available Online: 2024-04-28

Abstract

Abstract

To study the lipotoxicity of polyfluoroalkyl phosphate diesters(DiPAPs) to zebrafish, firstly, a three-dimensional quantitative structure-activity relationship(3D-QSAR) model of the binding of 15 perfluoroalkyl and polyfluoroalkyl substances(PFASs) with peroxisome proliferator-activated receptor β(PPARβ) was developed to predict the binding affinity of 6:2 and 8:2 DiPAPs, respectively. Afterward, the interactions between 6:2 and 8:2 DiPAPs and PPARβ were studied based on molecular docking. Finally, to verify the predicted results of the 3D-QSAR model, the effects of 6:2 and 8:2 DiPAPs on the expression of zebrafish PPARβ were investigated. The results show that the 50% inhibition concentration(pIC₅₀) of 6:2 and 8:2 DiPAPs was 3.73 mol/L and 3.63 mol/L, respectively, indicating their potential peroxisome proliferation activities. 6:2 and 8:2 DiPAPs could bind to PPARβ mainly through hydrogen bonding and hydrophobic interaction, and the binding activity of 6:2 DiPAP was higher than that of 8:2 DiPAP. After the exposure to 6:2 and 8:2 DiPAPs, the expressions of PPARβ were both significantly up-regulated. The expression in the 50 ng/L 6:2 DiPAP group was significantly higher than that in the 50 ng/L 8:2 DiPAP group, which was concordant with the predicted results by the 3D-QSAR model. In conclusion, 6:2 and 8:2 DiPAPs could induce lipotoxicity by affecting the expressions of zebrafish PPARβ. This study can provide scientific pieces of evidence for risk assessment of DiPAPs, such as a class of emerging PFASs, in the aquatic environment.
- polyfluoroalkyl phosphate diesters,
- 3D-QSAR,
- molecular docking,
- lipotoxicity,
- peroxisome proliferator-activated receptor

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References(39)

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