Comprehensive Interrogation of Metabolic and Bioenergetic Responses of Early-Staged Zebrafish (Danio rerio) to a Commercial Copper Hydroxide Nanopesticide

Abstract

The use of copper hydroxide nanopesticide can pose exposure risks to aquatic organisms. In this study, the toxicity of a copper hydroxide nanopesticide, compared to conventional copper sulfate at environmentally relevant doses, was evaluated using metabolomics and bioenergetic assays in embryonic zebrafish. At a copper concentration of 100 μg/L, the nanopesticide caused higher mortality and deformity compared to copper ions alone; despite higher copper accumulation, increased metallothionein and elevated ATP-binding cassette (ABC) transporter activity in zebrafish exposed to copper ions were observed. Both nanopesticide and copper ions reduced the abundance of metabolites of glycolysis and induced energetic stress in zebrafish. The nanopesticide also increased concentrations of several organic acids involved in the tricarboxylic acid (TCA) cycle and elevated the activity of isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, suggesting enhanced TCA cycle activity. Nanopesticide exposure depleted both glutamate and glutamine parallel to the upregulation of the TCA cycle. In addition, zebrafish exposed to the nanopesticide appeared to shift metabolism toward amino acid catabolism and lipid accumulation based upon altered expression profiles of glutaminase, glutamate dehydrogenase, fatty acid synthase, and acetyl-CoA carboxylase. Lastly, the ability of the ions to increase oxidative phosphorylation to alleviate energetic stress was reduced in the case of the nanopesticide. We hypothesize that, unlike copper ions alone, the nanopesticide induces higher toxicity to zebrafish because of increased protein catabolism. This study provides a comprehensive understanding of the risks of copper hydroxide nanopesticide exposure in relation to metabolic activity and mitochondrial function.

Surface Defects Regulate the in Vivo Bioenergetic Response of Earthworm Eisenia fetida Coelomocytes to Molybdenum Disulfide Nanosheets

“…The quantitative and visualized results of the JC-1 red/green fluorescence assay showed that DR-MoS 2 and Na 2 MoO 4 significantly induced depolarization of the mt△Ψ m at both low and high concentrations, whereas no impact was evident with DF-MoS 2 (Figures C, S6, S7). The transfer of electrons during mitochondrial respiration is accompanied by the establishment and dissipation of the membrane potential, which is essential for proper OXPHOS function. , The loss of mt△Ψ m after DR-MoS 2 and Na 2 MoO 4 exposure implies that the mitochondrial transmembrane potential was prematurely dissipated, which could directly affect the subsequent phosphorylation process …”

“…The inhibition of Mito-RETC complex I-mediated NADH electron flow by DR-MoS 2 could impede the mitochondrial membrane potential (mt△Ψ m ) formation and subsequent oxidative metabolic reactions. 52 Neither MoS 2 nanosheets nor molybdate at either concentration affected the activity of Mito-RECT complex II, the second component of OXPHOS (Figure 2E). However, Mito-RETC complex III activity was significantly inhibited after exposure to 100 mg Mo/L of DF-MoS 2 or DR-MoS 2 (p = 0.0482/p = 0.0022), although the inhibitory effect of DR-MoS 2 was more pronounced (p = 0.0413 for DF-MoS 2 vs DR-MoS 2 , t test) (Figure 2F).…”

“…The transfer of electrons during mitochondrial respiration is accompanied by the establishment and dissipation of the membrane potential, which is essential for proper OXPHOS function. 52,54 The loss of mt△Ψ m after DR-MoS 2 and Na 2 MoO 4 exposure implies that the mitochondrial transmembrane potential was prematurely dissipated, which could directly affect the subsequent phosphorylation process. 50 Mitochondrial fission and fusion under stress play a key role in maintaining mitochondrial function.…”

Metabolomic profiling of bovine leucocytes transformed by Theileria annulata under BW720c treatment

“…Glutamine and glutamic acid have similar biological functions. They can participate in the biosynthesis of α-ketoglutarate and can supplement citric acid, malic acid, and other tricarboxylic acid cycle intermediates [ 44 ]. Leucine can be a source of glutamine synthesis.…”

Scopoletin Induced Metabolomic Profile Disturbances in Zebrafish Embryos

“…Zebrafish ( Danio rerio ) has been widely used as a model organism for the evaluation of toxic effects [ 7 , 8 , 9 , 10 , 11 ]. In our previous study, we found that scopoletin had developmental toxicity to zebrafish embryos and the maximum non-lethal concentration (MNLC) was 18.5 μg/mL; and that scopoletin at 18.5 μg/mL could cause varying degrees of liver degeneration, pericardial edema, muscle degeneration, yolk sac retention, and reduced the blood flow of the zebrafish embryos.…”