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

نویسندگان

  • Ji Sun Baek
  • Longhou Fang
  • Andrew C. Li
  • Yury I. Miller
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

High fat plus high cholesterol diet lead to hepatic steatosis in zebrafish larvae: a novel model for screening anti-hepatic steatosis drugs.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD), characterized as excessive lipid accumulation within hepatocytes, is growing in prevalence. The exploitation of effective drugs for NAFLD has been proven challenging. Herein, we aimed to establish a dietary model of hepatic steatosis using transparent zebrafish larvae in which high-throughput chemical screens could be conducted. METHODS Ze...

متن کامل

Anti-hypercholesterolemic Effect of Berbamine Isolated from Rhizoma Coptidis in Hypercholesterolemic Zebrafish Induced by High-Cholesterol Diet

The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery ...

متن کامل

Anti-hypercholesterolemic Effect of Berbamine Isolated from Rhizoma Coptidis in Hypercholesterolemic Zebrafish Induced by High-Cholesterol Diet

The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery ...

متن کامل

High Cholesterol Diet Induces IL-1β Expression in Adult but Not Larval Zebrafish

Recently, it has been demonstrated that high cholesterol diet induced hypercholesterolemia and vascular lipid oxidation and accumulation in zebrafish larvae, suggesting that zebrafish is a new promising atherosclerosis model in addition to mouse models. However, up to date, there was no report regarding inflammatory cytokine expression during the lipid accumulation in zebrafish larva and adult ...

متن کامل

Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters.

Ezetimibe potently and selectively inhibits cholesterol absorption in the intestine, thereby reducing plasma cholesterol in preclinical models of hypercholesterolemia. Clinical trials have demonstrated that ezetimibe lowers LDL cholesterol and raises HDL cholesterol in humans. The effect of ezetimibe on other dyslipidemias, particularly hypertriglyceridemia, is not yet known. In the present stu...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 2012  شماره 

صفحات  -

تاریخ انتشار 2012