Investigating mitochondria-immune responses in zebrafish, Danio rerio (Hamilton, 1822): A case study with the herbicide dinoseb.

Xujia Zhang, Emma Ivantsova, Veronica Perez-Rodriguez, Fangjie Cao, Christopher L Souders, Christopher J Martyniuk

Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 2022 Jul

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The dinitrophenol herbicide dinoseb is an uncoupler of mitochondrial oxidative phosphorylation (OXPHOS). Studies in fish demonstrate impaired OXPHOS is associated with altered immune system responses and locomotor activity in fish. The objective of this study was to determine the effect of dinoseb on zebrafish (Danio rerio) during early stages of development. We measured oxygen consumption rates of embryos, transcripts related to OXPHOS, growth, and the immune system (cytokines and immune-signaling transcripts), and locomotor activity. We hypothesized that OXPHOS of fish would be impaired in vivo, leading to altered basal immune system expression and locomotor activity. Oxidative respiration assessments in embryos revealed that dinoseb decreased both mean basal respiration and oligomycin-induced ATP-linked respiration. Expression levels of cytochrome c oxidase complex IV, 3-hydroxyacyl-COA dehydrogenase and superoxide dismutase 1 were decreased in larvae following exposure to dinoseb while succinate dehydrogenase complex flavoprotein subunit A, insulin growth factor 1 (igf1) and igf2a mRNA were increased in abundance. Immune-related transcripts chemokine (C-X-C motif) ligand 1 and matrix metallopeptidase 9 (MMP-9) were decreased in expression levels while toll-like receptor 5a and 5b were increased in expression. In addition, a visual motor response test was conducted on both 6 and 7 dpf larvae to determine if dinoseb impaired locomotor activity. Dinoseb decreased locomotor activity in 7 dpf larvae but not 6 dpf. This study improves knowledge of toxicity mechanisms for dinoseb in early stages of fish development and demonstrates that mitochondrial toxicants may disrupt immune signaling in zebrafish. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Xujia Zhang, Emma Ivantsova, Veronica Perez-Rodriguez, Fangjie Cao, Christopher L Souders, Christopher J Martyniuk. Investigating mitochondria-immune responses in zebrafish, Danio rerio (Hamilton, 1822): A case study with the herbicide dinoseb. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 2022 Jul;257:109357