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Persistent Metabolic Changes Are Induced by 24 h Low-Dose Lead (Pb) Exposure in Zebrafish Embryos
Gwendolyn Cooper1, Ryan North2, Tyler Hunt-Smith2
1Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA.
International Journal of Molecular Sciences
|February 13, 2025
Summary
Lead (Pb) exposure alters zebrafish embryo metabolomes, affecting key metabolic pathways. This study identifies potential biomarkers for Pb exposure and reveals dose-dependent effects on cellular energy during development.
Area of Science:
- Environmental toxicology
- Developmental biology
- Metabolomics
Background:
- Lead (Pb) is a toxic heavy metal with known adverse effects.
- Limited research exists on the mechanistic impact of lead on development.
- Zebrafish embryos (Danio rerio) serve as a valuable model for studying chemical exposure effects.
Purpose of the Study:
- To investigate the impact of varying lead concentrations on the metabolome of developing zebrafish embryos.
- To identify potential biomarkers of lead exposure and understand dose-dependent effects.
- To elucidate the mechanistic pathways affected by lead during early development.
Main Methods:
- Zebrafish embryos were exposed to 5, 15, 150, and 1500 ppb lead for 24 hours post-fertilization.
- Untargeted metabolomics and multivariate analysis were employed to assess metabolic profiles.
- Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify lead accumulation.
Main Results:
- Lead exposure differentially altered the embryonic metabolome across various concentrations.
- Significant dysregulation was observed in biopterin, purine, alanine, and aspartate metabolism.
- Lead accumulation was confirmed in embryos, with observed decreases in oxidation-reduction ratios suggesting a hormetic effect at lower doses.
Conclusions:
- Lead exposure induces persistent, global changes in the developing zebrafish metabolome.
- Metabolomic profiles can serve as biomarkers for lead exposure, revealing dose-dependent relationships.
- Lead exposure impacts cellular energy metabolism and highlights aberrant processes in early development.

