Joint Hepatotoxicity Induced By Combined Exposure Of PBDE-209 And Cd

The detection rate of polybrominated diphenyl ethers and heavy metals is relatively high in water,air,soil.Polybrominated diphenyl ethers and heavy metals usually exist in the environment simultaneously,presenting combined exposed state.Therefore,it is need to pay attention to the more severe joint toxicity caused by combined exposure.Decabromodiphenyl(PBDE-209)and cadmium(Cd)were selected to study joint hepatotoxicity in this paper.There were two kinds of human hepatoma cell lines,HepG2 cells and SMMC-7721 cells used as experimental materials to study the joint effects by PBDE-209 and Cd on the liver cells.The contents and conclusions are as follows:1)Firstly separate exposure experiment of PBDE-209 or Cd was applied on human hepatoma cell lines and AB method was used to detect cell viability.We found that PBDE-209 has not shown significant concentration-dependent toxicity on the two kinds of cell lines in the study concentration range.However,significant concentration-dependent toxicity exised when the cells expose to Cd.The combined exposure concentrations successfully were screened according to the above results.2)The toxic effects on human hepatoma cell lines morphological,mitochondria and cell membranes induced by combined exposure of PBDE-209 and Cd were explored.The morphological changes were observed after combined exposure.Combined exposure were proved to cause mitochondrial damage extremely using MTT method.Further,no significant damage on cell membranes were observed in the concentration range investigated by LDH method.Therefore,the toxic effect may be not caused by cell membrane damage.3)Mitochondrial membrane potential of hepatocellular carcinoma cell lines was detected using JC-1 fluorescent probe after combined exposed of PBDE-209 and Cd.Combined with MTT experiment results,we confirmed that combined exposure of PBDE-209 and Cd could cause human hepatoma cell lines mitochondrial damage.Meanwhile,the flow cytometry experiment showed that combined exposure of PBDE-209 and Cd may cause apoptosis in human hepatoma cell lines.Thus,the joint hepatotoxicity of combined exposure of PBDE-209 and Cd may be induced by causing apoptosis of human hepatoma cell lines through mitochondrial pathway.4)ROS levels in hepatoma cell lines after combined exposed of PBDE-209 and Cdwere detected by using DCFH-DA probe.It was found that combined exposure of PBDE-209 and Cd could cause significantly increased ROS levels,which indicated that intracellular oxidative stress was increased.Increased ROS levels may be one of the reason for the cytotoxic effect,and may be one of the reason for the apoptosis.