ArticleDisease models & mechanisms2022
A multidimensional metabolomics workflow to image biodistribution and evaluate pharmacodynamics in adult zebrafish.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Transient exposure to bisphenol F in early life affects the metabolic health of adults.Exposome · 2026Article
- Intestine-derived sorbitol drives steatotic liver disease in the absence of gut bacteria.Science signaling · 2025Article
- Zebrafish in the spotlight: expanding Frontiers in toxicology and drug discovery.Toxicology research · 2025Review
- Standardization of zebrafish drug testing parameters for muscle diseases.Disease models & mechanisms · 2024Article
- Adult zebrafish as advanced models of human disease.Disease models & mechanisms · 2023Article
- Article
- Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem.Nature communications · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. We found that HCQ distributed to most organs in the adult zebrafish 24 h after addition of the drug to water, with the highest accumulation of both the drug and its metabolites being in the liver, intestine and kidney. Interestingly, HCQ treatment induced organ-specific alterations in metabolism. In the brain, for example, HCQ uniquely elevated pyruvate carboxylase activity to support increased synthesis of the neuronal metabolite, N-acetylaspartate. Taken together, this work validates a multidimensional metabolomics platform for evaluating the mode of action of a drug and its potential off-target effects in the adult zebrafish. This article has an associated First Person interview with the first author of the paper.
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Registered trials
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