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Zebrafish as model organisms for studying drug induced liver injury

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    Rights statement: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12408

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http://onlinelibrary.wiley.com/doi/10.1111/bcp.12408/abstract
Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
DOIs
StatePublished - 29 Apr 2014

Abstract

Drug induced liver injury (DILI) is a major challenge in clinical medicine and drug development. New models are needed for predicting which potential therapeutic compounds will cause DILI in humans, and new markers and mediators of DILI still need to be identified. This review will highlight the strengths and weaknesses of using zebrafish as a high throughput in vivo model for studying DILI. Although the zebrafish liver architecture is different to the mammalian liver, the main physiological processes remain similar. Zebrafish metabolize drugs using similar pathways as humans; they possess a wide range of cytochrome P450 enzymes enabling metabolic reactions including hydroxylation, conjugation, oxidation, demethylation and de-ethylation. Following exposure to a range of liver toxic drugs, the zebrafish liver develops histological patterns of injury comparable to mammals and liver injury biomarkers can be quantified in the zebrafish circulation. The zebrafish immune system is similar to mammals, but the zebrafish inflammatory response to DILI is not yet defined. To quantify DILI in zebrafish a wide variety of methods can be used including: visual assessment, quantification of serum enzymes and experimental serum biomarkers and scoring histopathology. With further development, the zebrafish may be a model that complements rodents and may have value for the discovery of new disease pathways and translational biomarkers.

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