Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis.
Steatohepatitis has recently been increasing as a cofactor influencing the progression of fibrosis, cirrhosis, adenoma and carcinoma in liver; however, the mechanisms by which it contributes to liver injury remain uncertain. We induced steatohepatitis in zebrafish embryos using thioacetamide (TAA). TUNEL assay revealed significant increasing of apoptosis in liver after 5 days post fertilization and the increasing of apoptosis was observed to be associated with the up-regulation of apoptotic genes such as, bad, bax, P-38a, caspase-3 and 8, and JNK-1. Histological sections by oil red O stain showed the accumulation of fatty droplets which causes the pushing of the nucleus towards one side. Up-regulation of steatosis markers such as, ACC, adiponectin, PTL, CEBP- alpha and beta, SREBP-1 was also observed. Furthermore, the elevation of glutathione peroxidase in TAA treated embryos indicated that TAA induces lipid peroxidation which leads to causes liver damage. Zebrafish has already been considered as a good human disease model and in this context; TAA-treated zebrafish may serve as a good animal model to study the molecular pathogenesis of steatohepatitis. Moreover, non-availability of specific drugs to prevent steatohepatitis, this animal model may serve as a powerful preclinical platform to study the therapeutic strategies and for evaluating chemoprevention strategies for this disease.
Amali
Aseervatham Anusha
AA
Laboratory of Marine Molecular Biology and Biotechnology 301, Institute Cellular and Organismic Biology, Academia Sinica, 128, Academia Road, Section 2, NanKang, Taipei, 11529, Taiwan.
Rekha
Ravikumar Deepa
RD
Lin
Cliff Ji-Fan
CJ
Wang
Wei-Lun
WL
Gong
Hong-Yi
HY
Her
Gour-Mour
GM
Wu
Jen-Leih
JL
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian; D005218:Fat Necrosis / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D006505:Hepatitis / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D013853:Thioacetamide / Q000009:adverse effects*; D015854:Up-Regulation / Q000235:genetics; D015027:Zebrafish
D051017:Apoptosis Regulatory Proteins; D013853:Thioacetamide