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Analysis of Liver Toxicity Markers in Danio rerio following Ethanol Exposure
Author(s) -
Chiari John B,
Charles Jamie M,
Laperche Jacob M,
McGinnis Courtney L
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1062.15
Subject(s) - zebrafish , danio , biology , xenobiotic , model organism , toxicity , drug metabolism , gene , transcriptome , lipid metabolism , metabolism , microbiology and biotechnology , biochemistry , gene expression , genetics , enzyme , chemistry , organic chemistry
Zebrafish have been used for many years in developmental and reproductive biology, yet little is still known about the adult zebrafish liver. Additionally, many of the mammalian liver cell types have yet to be characterized in zebrafish, including Kupffer cells, oval cells, and stellate cells. Also, there is minimal information available regarding zebrafish liver transporters and nuclear receptors. Therefore, it is important to understand the mechanism of xenobiotic metabolism in zebrafish to support their use as a model organism for studying the fate and biological effects of xenobiotics. The value of zebrafish as a model organism is based on a broad set of gene similarities (among fish species and humans) involved in metabolism and transportation of endogenous and exogenous chemicals. While there are molecular similarities between zebrafish and humans, there are also differences that may impact how compounds are metabolized. Therefore, it is absolutely necessary to investigate and validate the assumptions that zebrafish possess conserved genes, enzymes, and processes involved in all stages of metabolism. This study investigates the impact of ethanol exposure on liver toxicity markers in adult Danio rerio . Liver tissue from sham and ethanol injected fish were collected, pooled and RNA was isolated for qPCR. Relative expression levels for each gene were determined and normalized to βactin. Of the seventeen genes that were assessed, our results demonstrate a significant upregulation of the following genes following ethanol treatment: abcb4 (mdr3), abcc1(mrp1), abcc4(mrp4), abcc9(sur2), abcg5, mate1, oatp1 and slc4a2(ae2). Alcohol metabolism increases acetate production, a precursor for cholesterol and fatty acid synthesis. Historically, this increase in acetate levels driven by alcohol, is a contributor of hepatic steatosis (fatty liver). In a previous study conducted in the lab, zebrafish chronically exposured to ethanol displayed hallmark signs of hepatic steatosis. An upregulation in slc4a2, a sterol and cholesterol transporter aimed to eliminate dietary cholesterol, was found, consistent with the digestion of high levels of acetate. Furthermore, upregulation of abcc4, a prostaglandin transporter, is indicative of oxidative stress within the liver, caused by ethanol metabolism. Additionally, the upregulation of the other liver transporters would be consistent with normal hepatic ion flow during xenobiotic methabolism. Support or Funding Information Quinnipiac University: College of Arts and Sciences