Metabolomic Profiling Unveils the Impact of Non-Doped and Heteroatom-Doped Carbon Nanodots on Zebrafish (Danio rerio) Embryos

Abstract

Recently, concern has been raised over the transport, transformation, and fate of carbon nanodots (CNDs) after their release into the environment. Their toxicity towards organisms and humans has recently been addressed as an important issue. In this study, a metabolomic approach was employed to obtain an insight into the effect of CNDs (either pristine or doped with nitrogen and nitrogen/sulfur) on zebrafish. Embryos were exposed to concentrations corresponding to lethal concentration (LC) LC50 (550, 400, and 150 μg mL−1), LC50/2 (275, 200, and 75 μg mL−1), and LC50/4 (138, 100, and 38 μg mL−1) of the three CNDs (non-doped, N-doped, and N,S-codoped, respectively) to scrutinize the interactions of the CNDs with the larvae. Numerous differences in the metabolic pathways were recorded in all cases. Seven metabolic pathways were detected in the control larvae. When the larvae were exposed to concentrations equal to LC50, LC50/2, and LC50/4 of non-doped CNDs, 12, 12, and 3 metabolic pathways were detected, respectively. In the case of N-doped CNDs, 4, 7, and 4 pathways were detected, while in the case of N,S-codoped CNDs, 8, 5, and 5 pathways were detected when exposed to concentrations of LC50, LC50/2, and LC50/4, respectively. In all cases, certain metabolic pathways were altered while others were either down-regulated or up-regulated. Some of these changes include the activation of alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, butanoate metabolism, D-glutamine, and D-glutamate metabolism, glutathione metabolism, selenoamino acid metabolism, valine, leucine, and isoleucine degradation pathways. Moreover, the deactivation of starch and sucrose metabolism, the glycine, serine, and threonine metabolism, among others, were recorded. Our findings underline the importance to further study the impact of CNDs on marine organisms. As zebrafish has been shown to share many similarities with humans in bioprocesses and genome, it can be assumed that CNDs may also pose a threat to human health.

Optimization of a liquid chromatography-ion mobility-high resolution mass spectrometry platform for untargeted lipidomics and application to HepaRG cell extracts

“…Once the metabolites of interest have been annotated, a targeted method (hypothesis-driven) can be used in order to detect changes in the concentration of specific metabolites using reference standards [10]. Metabolomics studies can be carried out using different analytical platforms including GC-MS, nuclear magnetic resonance (NMR), LC-MS, or a combination of them (e.g., 1 H-NMR with LC-Orbitrap(MS)) [84]). An example of a multi-analytical platform used to study metabolite differences in zebrafish liver is the work of Ong et al [52].…”

Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges

“…Once the metabolites of interest have been annotated, a targeted method (hypothesis-driven) can be used in order to detect changes in the concentration of specific metabolites using reference standards [ 10 ]. Metabolomics studies can be carried out using different analytical platforms including GC-MS, nuclear magnetic resonance (NMR), LC-MS, or a combination of them (e.g., 1 H-NMR with LC-Orbitrap(MS)) [ 84 ]). An example of a multi-analytical platform used to study metabolite differences in zebrafish liver is the work of Ong et al [ 52 ].…”