Development of an Animal Model for Alcoholic Liver Disease in Zebrafish.
Alcoholic liver disease (ALD) continues to be a major cause of liver-related morbidity and mortality worldwide. To date, no zebrafish animal model has demonstrated the characteristic manifestations of ALD in the setting of chronic alcohol exposure. The aim of this study was to develop a zebrafish animal model for ALD. Male adult zebrafish were housed in a 1% (v/v) ethanol solution up to 3 months. A histopathological study showed the characteristic features of alcoholic liver steatosis and steatohepatitis in the early stages of alcohol exposure, including fat droplet accumulation, ballooning degeneration of the hepatocytes, and Mallory body formation. As the exposure time increased, collagen deposition in the extracellular matrix was observed by Sirius red staining and immunofluorescence staining. Finally, anaplastic hepatocytes with pleomorphic nuclei were arranged in trabecular patterns and formed nodules in the zebrafish liver. Over the time course of 1% ethanol exposure, upregulations of lipogenesis, fibrosis, and tumor-related genes were also revealed by semiquantitative and quantitative real-time reverse transcription-polymerase chain reaction. As these data reflect characteristic liver damage by alcohol in humans, this zebrafish animal model may serve as a powerful tool to study the pathogenesis and treatment of ALD and its related disorders in humans.
1 Department of Critical Care Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .|2 School of Medicine, College of Medicine, I-Shou University , Kaohsiung, Taiwan .|3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .
Jiun-Nong
JN
Lin
4 Department of Microbiology, Faculty of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan .
Lin-Li
LL
Chang
3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .
Chung-Hsu
CH
Lai
5 Department of Pathology, I-Shou University , Kaohsiung, Taiwan .
Kai-Jen
KJ
Lin
6 Department of Pharmacy, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .
Mei-Fang
MF
Lin
7 General Education Center, Meiho University , Pingtung, Taiwan .
Chih-Hui
CH
Yang
3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .
Hsi-Hsun
HH
Lin
8 School of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan .|9 Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung, Taiwan .|10 Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan .
Yen-Hsu
YH
Chen
D000818:Animals; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D015027:Zebrafish