Abstract
Organophosphorus flame retardants (OPFRs), a group of new emerging endocrine disruption chemicals, have been reported to cause metabolic disturbance. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated metabolic disruption. However, a comprehensive correlation between these two aspects of OPFR remains elusive. In the work reported here, 3 markers for morphological abnormality, and 7 markers of mitochondrial dysfunction were detected after treatment with two aryl-OPFRs (TCP and TPhP) and three chlorinated-OPFRs (TDCPP, TCPP, and TCEP) on hepatocyte. The two aryl-OPFRs and TDCPP can cause intracellular lipid accumulation at non-cytotoxic concentrations (<10 μM), while the other two chlorinated-OPFRs only caused lipid deposition at 10 μM. Furthermore, at the tested concentrations, all of them reduced mitochondrial (mito)-network numbers, enlarged mito-area/cells, and skewed mitoATP/glycoATP. Excluding TCEP, the other four chemicals induced mito-ROS and depleted mitochondrial membrane potential (MMP). Notably, only TCP, TPhP and TDCPP impeded mitoATP generation rate and mito-respiratory rate. Based on potency estimates, the capacity for lipid accumulation was significantly correlated with mito-network numbers (R2 = 0.6481, p < 0.01), mitoATP/glycoATP (R2 = 0.5197, p < 0.01), mitoROS (R2 = 0.7197, p < 0.01), and MMP (R2 = 0.7715, p < 0.01). Remarkably, the mito-respiratory rate (R2 = 0.8753, p < 0.01) exhibited the highest correlation. Thus, the more potent lipid inducers TPhP, TCP and TDCPP could be identified. The results of this study demonstrate that aryl-OPFRs are more potent in metabolic disruption than other esters examined. Metabolic disruption should be examined further for chemicals that have the capacity to counteract the aforementioned functions of mitochondrial.