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Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
Comprehensive analysis of organophosphorus flame retardant-induced mitochondrial abnormalities: Potential role in
Yifei Le1, Haiping Shen1, Zhen Yang1
1College of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.
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.
Insights
Organophosphorus flame retardants (OPFRs) can disrupt metabolism by affecting mitochondria. Aryl-OPFRs and TDCPP are potent inducers of lipid accumulation and mitochondrial dysfunction, highlighting their metabolic disruption capacity.
Area of Science:
- Environmental Toxicology
- Mitochondrial Biology
- Metabolic Disruptions
Background:
- Organophosphorus flame retardants (OPFRs) are emerging endocrine disruptors linked to metabolic disturbances.
- Mitochondrial dysfunction is a key indicator for evaluating chemical-mediated metabolic disruption.
- A comprehensive understanding of the correlation between OPFRs and mitochondrial dysfunction remains incomplete.
Purpose of the Study:
- To investigate the relationship between OPFR exposure and mitochondrial abnormalities.
- To assess the metabolic disruption potential of different OPFRs, including aryl and chlorinated compounds.
- To identify specific OPFRs that are potent inducers of lipid accumulation and mitochondrial dysfunction.
Main Methods:
- Hepatocytes were treated with two aryl-OPFRs (TCP, TPhP) and three chlorinated-OPFRs (TDCPP, TCPP, TCEP).
- Morphological and mitochondrial dysfunction markers were analyzed, including lipid accumulation, mitochondrial network, ATP levels, ROS production, and membrane potential.
- Correlation analyses were performed to link lipid accumulation capacity with mitochondrial dysfunction markers.
Main Results:
- Aryl-OPFRs (TCP, TPhP) and TDCPP induced significant intracellular lipid accumulation at non-cytotoxic concentrations.
- All tested OPFRs reduced mitochondrial network numbers, increased mitochondrial area, and altered ATP distribution.
- Mitochondrial respiratory rate showed the highest correlation with lipid accumulation capacity, identifying TPhP, TCP, and TDCPP as potent inducers.
Conclusions:
- Aryl-OPFRs demonstrate greater potency in metabolic disruption compared to other OPFR esters examined.
- Mitochondrial dysfunction, particularly impaired respiratory rate, is a strong indicator of OPFR-induced metabolic disruption.
- Further investigation into chemicals affecting mitochondrial functions is crucial for understanding metabolic disruption.
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