Zebrafish as a Model to Study Cholestatic Liver Diseases

Pham, Duc-Hung; Yin, Chunyue

doi:10.1007/978-1-4939-9420-5_18

Cited by 20 publications

(25 citation statements)

References 44 publications

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“…The homogenate of each replicate was spun at room temperature at 20000 g for 30 min. The supernatant was collected, air-dried in a fume hood overnight, and subjected to bile salt quantification using the enzyme-cycling method based bile acid detection kit (Diazyme, DZ042A) as described previously (14).…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…The zebrafish (Danio rerio) has emerged as a powerful model for studying bile salt-related liver diseases due to their conserved mechanisms of liver and intestinal development and bile secretion, facile genetic and transgenic manipulations, and ease of monitoring host-microbiota interactions and other physiological processes in vivo (11)(12)(13)(14). The genome of zebrafish possesses orthologs of many mammalian genes known to be involved in bile salt homeostasis, including bile salt transporters, bile salt synthesis enzymes, and FXR (7,12,15,16).…”

Section: Introductionmentioning

confidence: 99%

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Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Wen

Mercado

Volland

et al. 2020

Preprint

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Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occurs in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcription factor Farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C27 bile alcohol and a C24 bile acid which undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a non-mammalian vertebrate model for studying bile salt metabolism and Fxr signaling.

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Section: Supplementary Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Wen

Mercado

Volland

et al. 2020

Preprint

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“…Despite the anatomical differences between the species, cells constituting the liver are the same as in mammals. Pathological changes, such as cholestasis 65 , steatosis 66 , necrosis 67 , and hepatic tumors 68 have also been reported in zebrafish.…”

Section: Examples Of Applicationsmentioning

confidence: 99%

Application of zebrafish to safety evaluation in drug discovery

Miyawaki

2020

J Toxicol Pathol

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Traditionally, safety evaluation at the early stage of drug discovery research has been done using in silico , in vitro , and in vivo systems in this order because of limitations on the amount of compounds available and the throughput ability of the assay systems. While these in vitro assays are very effective tools for detecting particular tissue-specific toxicity phenotypes, it is difficult to detect toxicity based on complex mechanisms involving multiple organs and tissues. Therefore, the development of novel high throughput in vivo evaluation systems has been expected for a long time. The zebrafish ( Danio rerio ) is a vertebrate with many attractive characteristics for use in drug discovery, such as a small size, transparency, gene and protein similarity with mammals (80% or more), and ease of genetic modification to establish human disease models. Actually, in recent years, the zebrafish has attracted interest as a novel experimental animal. In this article, the author summarized the features of zebrafish that make it a suitable laboratory animal, and introduced and discussed the applications of zebrafish to preclinical toxicity testing, including evaluations of teratogenicity, hepatotoxicity, and nephrotoxicity based on morphological findings, evaluation of cardiotoxicity using functional endpoints, and assessment of seizure and drug abuse liability.

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“…The adenomatous polyposis coli ( APC ) gene has a role in development and regeneration, and the APC ‐mutant zebrafish has proved useful in studying liver developmental and regeneration pathways (Goessling et al, 2008). Zebrafish mutants to study hepatocellular carcinoma (Cox, Tsomides, et al, 2016; Evason et al, 2015; Mudbhary et al, 2014) and biliary disease (Pham & Yin, 2019) have also been well explored.…”

Section: Genetic Models Of Zebrafish For Liver Diseasesmentioning

confidence: 99%

Zebrafish: An emerging model system to study liver diseases and related drug discovery

Katoch

Patial

2020

J of Applied Toxicology

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The zebrafish has emerged as a powerful vertebrate model for studying liverassociated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the highthroughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real-time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liverrelated studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate-like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell-based and mammalian models.

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Zebrafish as a Model to Study Cholestatic Liver Diseases

Cited by 20 publications

References 44 publications

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Application of zebrafish to safety evaluation in drug discovery

Zebrafish: An emerging model system to study liver diseases and related drug discovery

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