The zebrafish embryo as a model for chemically-induced steatosis: A case study with three pesticides

There is an increasing incidence and prevalence of fatty liver disease in the western world, with steatosis as the most prevalent variant. Known causes of steatosis include exposure to food-borne chemicals, and overconsumption of alcohol, carbohydrates and fat, and it is a well-known side effect of...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2024-11, Vol.508, p.153927, Article 153927
Main Authors: Heusinkveld, Harm J., Zwart, Edwin P., de Haan, Angela, Braeuning, Albert, Alarcan, Jimmy, van der Ven, Leo T.M.
Format: Article
Language:English
Subjects:
Animals
Danio rerio
Disease Models, Animal
Dose-Response Relationship, Drug
Embryo, Nonmammalian - drug effects
Fatty Liver - chemically induced
Fluorescent imaging
Mixture toxicology
NAFLD
Pesticides - toxicity
Triglycerides - metabolism
Whole-organism
Zebrafish
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Summary:There is an increasing incidence and prevalence of fatty liver disease in the western world, with steatosis as the most prevalent variant. Known causes of steatosis include exposure to food-borne chemicals, and overconsumption of alcohol, carbohydrates and fat, and it is a well-known side effect of certain pharmaceuticals such as tetracycline, amiodarone and tamoxifen (drug-induced hepatic steatosis). Mechanistic knowledge on chemical-induced steatosis has greatly evolved and has been organized into adverse outcome pathways (AOPs) describing the chain of events from first molecular interaction of a substance with a biological system to the adverse outcome, intrahepatic lipid accumulation. In this study, three known steatosis-inducing pesticides (imazalil, clothianidin, and thiacloprid) were tested for their ability to induce hepatic triglyceride accumulation in the zebrafish (Danio rerio) embryo (ZFE) at 5 days post fertilization, both as single compounds and equipotent binary mixtures. The results indicate that the ZFE is very well applicable as a higher tier testing model to confirm effects in downstream key events in AOPs, that is, chemically-induced triglyceride accumulation in the whole organism and production of visible steatosis. Moreover, dose addition could be concluded for binary mixtures of substances with similar and with dissimilar modes of action.
ISSN:0300-483X
1879-3185
1879-3185
DOI:10.1016/j.tox.2024.153927