Cargando…

Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet

Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD) develop hypercholesterolemia and are characterized by profound lipoprotein oxidation...

Descripción completa

Detalles Bibliográficos
Autores principales: Baek, Ji Sun, Fang, Longhou, Li, Andrew C., Miller, Yury I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369394/
https://www.ncbi.nlm.nih.gov/pubmed/22693663
http://dx.doi.org/10.1155/2012/564705
_version_ 1782235050802151424
author Baek, Ji Sun
Fang, Longhou
Li, Andrew C.
Miller, Yury I.
author_facet Baek, Ji Sun
Fang, Longhou
Li, Andrew C.
Miller, Yury I.
author_sort Baek, Ji Sun
collection PubMed
description Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD) develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia.
format Online
Article
Text
id pubmed-3369394
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-33693942012-06-12 Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet Baek, Ji Sun Fang, Longhou Li, Andrew C. Miller, Yury I. Cholesterol Research Article Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD) develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia. Hindawi Publishing Corporation 2012 2012-05-30 /pmc/articles/PMC3369394/ /pubmed/22693663 http://dx.doi.org/10.1155/2012/564705 Text en Copyright © 2012 Ji Sun Baek et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Baek, Ji Sun
Fang, Longhou
Li, Andrew C.
Miller, Yury I.
Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title_full Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title_fullStr Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title_full_unstemmed Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title_short Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
title_sort ezetimibe and simvastatin reduce cholesterol levels in zebrafish larvae fed a high-cholesterol diet
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369394/
https://www.ncbi.nlm.nih.gov/pubmed/22693663
http://dx.doi.org/10.1155/2012/564705
work_keys_str_mv AT baekjisun ezetimibeandsimvastatinreducecholesterollevelsinzebrafishlarvaefedahighcholesteroldiet
AT fanglonghou ezetimibeandsimvastatinreducecholesterollevelsinzebrafishlarvaefedahighcholesteroldiet
AT liandrewc ezetimibeandsimvastatinreducecholesterollevelsinzebrafishlarvaefedahighcholesteroldiet
AT milleryuryi ezetimibeandsimvastatinreducecholesterollevelsinzebrafishlarvaefedahighcholesteroldiet