| Autor: |
Zheng S; Schering-Plough Research Institute, Kenilworth, NJ 07033, USA., Hoos L, Cook J, Tetzloff G, Davis H Jr, van Heek M, Hwa JJ |
| Jazyk: |
angličtina |
| Zdroj: |
European journal of pharmacology [Eur J Pharmacol] 2008 Apr 14; Vol. 584 (1), pp. 118-24. Date of Electronic Publication: 2008 Feb 12. |
| DOI: |
10.1016/j.ejphar.2008.01.045 |
| Abstrakt: |
Ezetimibe is a novel cholesterol and plant sterol absorption inhibitor that reduces plasma low-density lipoprotein-cholesterol by selectively binding to the intestinal cholesterol transporter, Niemann-Pick C1-Like 1. Mice deficient in Niemann-Pick C1-Like 1 are protected from high fat/cholesterol diet-induced fatty liver as well as hypercholesterolemia. The object of the present study was to determine whether ezetimibe treatment could reduce hepatic steatosis in diet-induced obese mice. C57BL/6J mice were fed a high fat/cholesterol containing semi-purified diet (45% Kcal fat and 0.12% cholesterol) for 7 months after weaning. These mice were not only obese, but also developed hepatomegaly and hepatic steatosis, with varying degrees of liver fibrosis and steatohepatitis. About 87% of the mice on the high fat/cholesterol diet for 7 months had elevated plasma alanine aminotransferase activity, a biomarker for non-alcoholic fatty liver disease. Chronic administration of ezetimibe for 4 weeks significantly reduced hepatomegaly by decreasing hepatic triglyceride, cholesteryl ester and free cholesterol in diet-induced obese mice fed high fat/cholesterol diet for 7 months. Chronic ezetimibe treatment also significantly decreased plasma alanine aminotransferase activity. These results suggest that ezetimibe may be a novel treatment for high fat/cholesterol-induced non-alcoholic fatty liver disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect