The Effects of Pretreatment with Atorvastatin, Fenofibrate, or Both Drugs in a Mouse Model of Acute Lipemia Induced by the General Lipase Inhibitor Poloxamer 407

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发表日期：

2024年9月1日

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T. A. Korolenko,
T. P. Johnston,
N. V. Tamkovich,
V. A. Vavilin,
N. P. Bgatova,
I. D. Ivanov,
G. S. Russkikh,
E. V. Koldysheva,
E. C. Korolenko,
V. I. Kapustina,
S. I. Makarova,
N. V. Goncharova,
M. M. Gevorgyan,
V. M. Loginova

摘要

Abstract

Dyslipidemia is a well-known risk factor for the development of cardiovascular diseases and atherosclerosis. The effects of combined pretreatment with atorvastatin and fenofibrate (Tricor) were studied in a mouse model of acute lipemia induced by a general lipase inhibitor, poloxamer 407 (P-407, 250 mg/kg). This lipemia is characterized by significantly increased serum levels of triglycerides (TG), low-density lipoprotein (LDL) cholesterol, together with decreased concentration of high-density lipoprotein (HDL) cholesterol. Atorvastatin pretreatment had a hypolipidemic effect, decreasing concentrations of LDL cholesterol and increasing HDL cholesterol. Pretreatment of mice with fenofibrate decreased TG level, increasing HDL cholesterol. Combined pretreatment with atorvastatin and fenofibrate decreased TG and total cholesterol. Elevation of the serum cystatin C level was found in control and lipemic mice pretreated with atorvastatin, fenofibrate, or both. Liver expression of lysosomal acid lipase increased in atorvastatin- or/and fenofibrate-pretreated groups of lipemic mice. It was concluded that increased expression of lysosomal acid lipase is related to the removal of lipid droplets from hepatocytes, thus preventing acute lipemia. Lastly, cystatin C may be a “theranostic” biomarker for hypolipidemic drugs.