Image-based Tissue Informatics -- TAA induced
Fish Hepatotoxicity Model
Hepatotoxicity is chemical-driven liver damage. In the drug development industry,
hepatic toxicity seems to be the major problems causing market withdrawal. Drug
discovery involves a complex iterative process of biochemical and cellular assays, with
final validation in animal models, and ultimately in humans. Mammalian models are
expensive, laborious and consume large quantities of precious compounds. In the past
few decades, zebrafish are beginning to be used at various stages of the drug discovery
process and can be a useful and cost-effective alternative to some mammalian models.
Medaka, like Zebrafish, is one of the small teleost fish that has long been a favorite in
home aquariums due to its hardy nature. It presents many organs and cell types similar to
that of mammals. In this project, we aimed to establish an in vivo model for the screening
of hepatotoxicity using medaka fish. Thioacetamide (TAA), a commonly used model
toxin for the study of hepatotoxicity, hepatocarcinogenicity and cellular response to
injury, was used for the production of hepatic lesion in medaka fish. The most effective
thioacetamide concentrations for chronic and acute liver damage were found out by a
series of treatments. RT-PCR and H&E staining methods were used to examine the
mRNA expression level of certain genes and the architecture of tissue in damaged liver.
We have also developed and applied Two-photon Excitation Fluorescence/ Second
Harmonic Generation microscopy for imaging of unstained liver tissue. Quantitative
signals have been obtained from hepatocytes and extracellular matrix. Comprehensive
imaging processing algorithms were developed for quantification of collagen content and
cell necrosis.