Zebrafish Hepatoxicity Assays

Drug-induced liver injury (DILI) represents a major challenge for the pharmaceutical industry and regulatory authorities, as it is a major problem in both the early and later stages of the drug development process, and the most common cause of post-marketing warnings and withdrawals. Its strategic location and outstanding role in the metabolism of xenobiotics renders the liver particularly susceptible to potential toxic effects of a drug and/or its metabolites. Thus, to set up better tools to screen for DILI of large compound libraries in the early stages of drug development will be allowed to get a better understanding of hepatotoxicity.

Recently, zebrafish embryos and larvae have become a popular model in most aspects of safe high-throughput pharmacology and toxicity screens as well as in disease models, especially for investigation of drug effects on liver structure and function. Concerning zebrafish liver, it has been vascularized by 3 days post-fertilization, functioning and excreting various chemicals. Compared to mammals, zebrafish larvae can catalyze similar phase 1 and phase 2 reactions and metabolic pathways for some drugs. Zebrafish have a wide range of cytochrome P450 enzymes that allow metabolic reactions including hydroxylation, oxidation, conjugation, demethylation and de-ethylation. Following exposure to a range of hepatotoxic drugs, the zebrafish liver develops histological patterns of injury compared to those of mammalian liver, and biomarkers for liver injury can be quantified in the zebrafish circulation. In a word, it can serve as a bridge between the in vivo and in vitro models to cover the complete biological complexity, and its ability for high-throughput screening, makes zebrafish a potential model for liver toxicity assay.

Figure 1. The visual phenotype of hepatotoxicity in zebrafish at 120 hpf after exposure to drugs/compounds from 72 to 120 hpf. (He J H, et al., 2013)

Our Developmental Hepatoxicity Assessment in Zebrafish

With years of experience and advanced technologies, Creative Biogene has developed several approaches to utilize zebrafish in hepatoxicity screening, including visual assessment of gross and microscopic morphological changes, hepatic excretory tests, serum enzyme and biomarker tests, and assessment of alterations in chemical constituents of the liver.

Gross/subgross visual phenotypic assessment
Liver histopathology
Liver function assay
Hepatic excretory tests
Screening of potential diagnostic biomarker candidates
Changes in protein and mRNA transcription relevant to cell apoptosis
Metabolic pathway enrichment analysis

Our Advantages

Wide ranges of detection technologies
Easy and flexible workflow
Advanced high-content screening equipment
Excellent predictability

References

Mesens N, et al. Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?. Journal of Applied Toxicology, 2015, 35(9): 1017-1029.
Zhao C, et al. Hepatotoxicity evaluation of Euphorbia kansui on zebrafish larvae in vivo. Phytomedicine, 2019, 62: 152959.
Vliegenthart A D B, et al. Zebrafish as model organisms for studying drug-induced liver injury. British journal of clinical pharmacology, 2014, 78(6): 1217-1227.
He J H, et al. A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity. Journal of pharmacological and toxicological methods, 2013, 67(1): 25-32.
Caballero M V, Candiracci M. Zebrafish as screening model for detecting toxicity and drugs efficacy. Journal of Unexplored Medical Data, 2018, 3(4): 1-14.

For research use only. Not intended for any clinical use.

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