The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart
| Autor: | Anna A Monoszon, V. K. Spiridonov, Ivan V. Brak, Marina S. Cherkanova, Svetlana Ya. Zhanaeva, Natalia Alexandrovna Zhukova, Natalia A. Tuzikova, F. V. Tuzikov, Thomas P. Johnston, Yana A. Kisarova, Tatyana A. Korolenko, Elena E. Filjushina, Tatyana V. Alexeenko |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Physiology medicine.medical_treatment Lipoproteins Poloxamer Pharmacology Triglycerides blood Lipoproteins VLDL Mice Physiology (medical) medicine Matrix metalloproteases Animals Liver immunology Triglycerides Dyslipidemias Protease Chemistry Myocardium General Medicine Atherosclerosis Cathepsins Cholesterol blood Disease Models Animal Cholesterol Hexosaminidases Lipoproteins IDL Liver Poloxamer 407 Immunology Hypertension Metalloproteases Mice Inbred CBA lipids (amino acids peptides and proteins) Liver ultrastructure medicine.drug Foam Cells |
| Zdroj: | Canadian journal of physiology and pharmacology. 90(11) |
| ISSN: | 1205-7541 |
| Popis: | The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL1–3-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL1–2-C and VLDL3–5-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL2-C and HDL3-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|