NDLI: Functional xenobiotic metabolism and efflux transporters in trout hepatocyte spheroid cultures

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Functional xenobiotic metabolism and efflux transporters in trout hepatocyte spheroid cultures

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Toxicology Research Vol - 4 Issue - 1

Toxicology Research Vol -3

Toxicology Research Vol -2

Toxicology Research Vol -1

Functional xenobiotic metabolism and efflux transporters in trout hepatocyte spheroid cultures

Content Provider	Royal Society of Chemistry (RSC)
Author	Owen, Stewart F. Uchea, Chibuzor Chipman, J. Kevin
Copyright Year	2015
Abstract	Prediction of xenobiotic fate in fish is important for the regulatory assessment of chemicals under current legislation. Trout hepatocyte spheroids are a promising in vitro model for this assessment. In this investigation, the gene expression and function for xenobiotic metabolism and cellular efflux were characterised. Using fluorescence, transport and real time PCR analysis, the expression and functionality of a variety of genes related to xenobiotic metabolism and drug efflux were assessed in a range of trout hepatocyte culture preparations. Significantly greater levels of expression of genes involved in xenobiotic metabolism and efflux were measured in spheroids (which have been shown to remain viable in excess of 30 days), compared to hepatocytes cultured using conventional suspension and monolayer culture techniques. A transient decline in the expression of genes related to both xenobiotic metabolism and transport was determined during spheroid development, with a subsequent recovery in older spheroids. The most mature spheroids also exhibited an expression profile most comparable to that reported in vivo. Functionality of efflux transporters in spheroids was also demonstrated using fluorescent markers and specific inhibitors. In conclusion, the more physiologically relevant architecture in spheroid cultures provides a high functional integrity in relation to xenobiotic metabolism and efflux. Together with the enhanced gene expression and longevity of the model, hepatocytes in spheroid culture may prove to be an accurate alternative model to study the mechanisms of these processes in fish liver and provide an assay to determine the bioaccumulation potential of environmental contaminants.
Starting Page	494
Ending Page	507
Page Count	14
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	4
Issue Number	2
Journal	Toxicology Research
DOI	10.1039/c4tx00160e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Polymerase chain reaction Hepatocyte Gene Bioaccumulation Liver Drug metabolism Fluorescence Spheroid Xenobiotic
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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