Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 422, Issue 1, Pages 22-27Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.04.087
Keywords
NASH; Ezetimibe; Medaka; Inflammation
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Funding
- Japan Society for the Promotion of Science [22659148, 23659398]
- Japan Science and Technology Agency
- Ministry of Health, Labour and Welfare
- Grants-in-Aid for Scientific Research [23659398, 22659148] Funding Source: KAKEN
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Purpose: We previously developed medaka non-alcoholic steatohepatitis (NASH) model. The model showed similar histology with human NASH so we analyzed the effect of drug using medaka NASH activity score (MNAS). In this study we analyzed the effect of ezetimibe, a small intestine cholesterol transporter inhibitor, on NASH. Methods: Medaka NASH model showed steatohepatits with infiltration of D-PAS positive inflammatory cell. In this study we induced medaka NASH and compared the effect of ezetimibe on medaka NASH by HFD. Results: As compared with the HFD group, ezetimibe reduced total cholesterol and triacyglycerol in the blood. But concerning with liver quantity of fatty acids in the liver were significantly decreased by ezetimibe. Genes related with fatty acid metabolism in liver was also decreased by ezetimibe administration. On histological observations of the liver, increases in the number of inflammatory cells and MNAS were inhibited. With this decrease of fatty acid in liver, medaka NASH was improved by ezetimibe. Conclusion: Ezetimibe was clarified as a useful drug to improve NASH. (C) 2012 Elsevier Inc. All rights reserved.
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