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

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2024-11-05 DOI:10.1134/S1990750823600474

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

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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.

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阿托伐他汀、非诺贝特或两种药物的预处理对普通脂肪酶抑制剂聚氧乙烯-407 诱导的急性脂肪血症小鼠模型的影响

众所周知，血脂异常是导致心血管疾病和动脉粥样硬化的危险因素。研究人员在一种由普通脂肪酶抑制剂多聚酶 407（P-407，250 毫克/千克）诱发的急性脂血症小鼠模型中研究了阿托伐他汀和非诺贝特（Tricor）联合预处理的效果。这种脂血症的特点是血清中甘油三酯（TG）和低密度脂蛋白（LDL）胆固醇水平明显升高，同时高密度脂蛋白（HDL）胆固醇浓度降低。阿托伐他汀预处理具有降血脂作用，可降低低密度脂蛋白胆固醇的浓度，提高高密度脂蛋白胆固醇的浓度。对小鼠进行非诺贝特预处理可降低总胆固醇水平，增加高密度脂蛋白胆固醇。阿托伐他汀和非诺贝特联合预处理可降低总胆固醇和总胆固醇。在对照组和使用阿托伐他汀、非诺贝特或两者进行预处理的高脂血症小鼠中发现血清胱抑素 C 水平升高。阿托伐他汀或/和非诺贝特预处理组的高脂血症小鼠肝脏溶酶体酸性脂肪酶表达增加。结论是溶酶体酸性脂肪酶表达的增加与清除肝细胞中的脂滴有关，从而防止了急性脂血症的发生。最后，胱抑素 C 可能是降血脂药物的 "治疗 "生物标志物。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.