Toxic Effects And Mechanism Of Tetrabromobisphenol A On Human Normal Liver Cells(L02)

Tetrabromobisphenol A(TBBPA)has good flame retardancy and heat resistance and is widely used in electrical appliances,furniture,plastics and electronic products.Due to the mass production of TBBPA,the product can be released into the environment through various channels after being discarded,and the presence of TBBPA is detected in environmental media such as soil,water sediment and atmosphere,and in living organisms.In order to explore the harm of TBBPA to human health,human normal liver cell L02 cells were selected as model organisms to study the toxic effects of TBBPA on L02 cells.The results showed that TBBPA can alter the morphology of L02 cells.As the concentration of TBBPA increases,the number of L02 cells decreases and the activity decreases.Compared with the control group,40 ?M TBBPA treated for 12 h,the ROS concentration increased by 2.8 times,the GSH content decreased to 0.24 times,the GSSG content increased by 2.3 times.The MDA content increased by 2.9 times and the cells were in an oxidative stress state.The relative amount of tail DNA was 6.5 times higher than that of the control group,indicating that the cellular DNA was damaged.The results showed that the JC-1 monomer polymer ratio decreased from 1.36±0.07 to 0.44±0.07 after exposure to 5-40?M TBBPA for 48 h.After 40?M TBBPA treatment for 48 h the mRNA expression level of Bcl-2 decreased by 0.53±0.04,Bax increased by 3.15±0.08,and Caspase-3 increased by 5.28±1.06.The ratio of Bcl-2 protein concentration decreased to 0.26±0.02,Bax,Caspase-3,and Cyt C increased to 0.77±0.04,0.77±0.06,and 0.54±0.03.The apoptotic rate was increased by 6.1-fold.TBBPA stimulates MMP in L02 cells to reduce mitochondrial membrane damage,Cyt C release to cytoplasm,mRNA and protein expression of anti-apoptotic protein(Bcl-2)and proapoptotic protein(Bax),activate Caspase-9,activate downstream Caspase-3,TBBPA can induce apoptosis of L02 cells.The results showed that compared with the non-NAC group,the ROS decreased by(56.1±7.8)%,JC-1 monomer decreased by(38.7±2.7)%,and apoptosis decreased by 15.7%.Thus,it is proved that apoptosis is closely related to the increase of intracellular ROS content.After TBBPA induces an increase in ROS content in L02 cells,it activates the intracellular Nrf2 pathway,and activated Nrf2 enters the nucleus to enhance the activity of antioxidant enzymes,thereby exerting its own antioxidant damage.