Differential mitochondrial dysregulation by exposure to individual organochlorine pesticides (OCPs) and their mixture in zebrafish embryos
2021
Lee, Hyojin | Ko, Eun | Shin, Sooim | Choi, Moonsung | Kim, Ki-Tae
Organochlorine pesticides (OCPs) have been reported to cause mitochondrial dysfunction. However, most studies reported its mitochondrial toxicity with respect to a single form, which is far from the environmentally relevant conditions. In this study, we exposed zebrafish embryos to five OCPs: chlordane, heptachlor, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), β-hexachlorocyclohexane (β-HCH), and hexachlorobenzene (HCB), as well as an equal ratio mixture of these OCPs. We evaluated mitochondrial function, including oxygen consumption, the activity of mitochondrial complexes, antioxidant reactions, and expression of genes involved in mitochondrial metabolism. Oxygen consumption rate was reduced by exposure to chlordane, and β-HCH, linking to the increased activity of specific mitochondrial complex I and III, and decreased GSH level. We found that these mitochondrial dysfunctions were more significant in the exposure to the OCP mixture than the individual OCPs. On the mRNA transcription level, the individual OCPs mainly dysregulated the metabolic cycle (i.e., cs and acadm), whereas the OCP mixture disrupted the genes related to mitochondrial oxidative phosphorylation (i.e., sdha). Consequently, we demonstrate that the OCP mixture disrupts mitochondrial metabolism by a different molecular mechanism than the individual OCPs, which warrants further study to evaluate mitochondrial dysregulation by chronic exposure to the OCP mixture.
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