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Membrane Toxicity And Thyroid Interference Effects Of Brominated Flame Retardant Decabromodiphenylethane

Posted on:2020-06-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q LiuFull Text:PDF
GTID:2404330596487921Subject:Pharmaceutical
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With the widespread use of Decabromodiphenyl Ethane(DBDPE),its toxicity research has gradually attracted people's attention.Previous studies have shown that DBDPE has potential endocrine toxicity,liver toxicity,neurotoxicity and reproductive developmental toxicity.Therefore,in our work,the toxicity of DBDPE to cell membranes and the molecular mechanism of interaction with thyroid hormone receptors were studied by means of cell exposure,polarization fluorescence and molecular dynamics simulation.(1)The cell membrane toxicity of decabromodiphenylethane was determined by cell exposure experiments.It was found that DBDPE increased its membrane toxicity in a concentration-and time-dependent manner.Further using the method of fluorescence polarization,artificially imitating the cell membrane as a model,it was found that the presence of DBDPE significantly reduced the cell membrane fluidity.Finally,a phospholipid bilayer with dipalmitoylphosphatidylcholine(DPPC)as the main component was constructed by the molecular dynamics simulation method to simulate the change of physicochemical properties of phospholipid bilayer in the presence of different concentrations of DBDPE.Through simulation,it was found that DBDPE molecules can enter the cell membrane and accumulation,and with the increasing of its concentration,the phospholipid bilayer structure changes significantly,and the fluidity of the membrane shown a significant downward trend.(2)The interference effects of decabromodiphenylethane on thyroid hormone receptor was studied based on the molecular dynamics simulation method.The typical brominated flame retardant PBDE209 was used as a control to discuss the binding mode of DBDPE and PBDE209 to thyroid hormone receptors.So that,we discussed the mechanism of DBDPE on thyroid hormone interference at the molecular level.These studies are helpful in understanding the in vivo processes of DBDPE and provide reliable data and scientific evidence for subsequent safety assessments and risk assessments.
Keywords/Search Tags:Decabromodiphenylethane, Membrane, Thyroid Hormone Receptor, Molecular Dynamics Simulation
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