Lee Hyojin, Ko Eun, Shin Sooim, Choi Moonsung, Kim Ki-Tae
Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul, 01811, Republic of Korea.
Department of Biotechnology and Bioengineering, Chonnam National University, Gwangju 61186, Republic of Korea; Interdisciplinary Program of Bioenergy and Biomaterials Graduate School, Chonnam National University, Gwangju, 61186, Republic of Korea.
Environ Pollut. 2021 May 15;277:115904. doi: 10.1016/j.envpol.2020.115904. Epub 2020 Oct 20.
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.
据报道，有机氯农药（OCPs）会导致线粒体功能障碍。然而，大多数研究报告的是其对单一形式的线粒体毒性，这与环境相关条件相差甚远。在本研究中，我们将斑马鱼胚胎暴露于五种有机氯农药：氯丹、七氯、对，对'-二氯二苯三氯乙烷（p，p'-DDT）、β-六氯环己烷（β-HCH）和六氯苯（HCB），以及这些有机氯农药的等比例混合物中。我们评估了线粒体功能，包括氧气消耗、线粒体复合物的活性、抗氧化反应以及参与线粒体代谢的基因表达。暴露于氯丹和β-HCH会降低氧气消耗率，这与特定线粒体复合物I和III的活性增加以及谷胱甘肽（GSH）水平降低有关。我们发现，与单独暴露于单一有机氯农药相比，暴露于有机氯农药混合物时这些线粒体功能障碍更为显著。在mRNA转录水平上，单一有机氯农药主要使代谢循环（即cs和acadm）失调，而有机氯农药混合物则破坏了与线粒体氧化磷酸化相关的基因（即sdha）。因此，我们证明有机氯农药混合物通过与单一有机氯农药不同的分子机制破坏线粒体代谢，这值得进一步研究以评估长期暴露于有机氯农药混合物引起的线粒体失调。
