title: The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.
abstract: 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.
authors.affiliation: Institute of Physiology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Timakov Street 4, 630117, Russian Federation. t.a.korolenko@physiol.ru
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Korolenko
authors.forename: Fedor V
authors.initials: FV
authors.lastname: Tuzikov
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Johnston
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Tuzikova
authors.forename: Yana A
authors.initials: YA
authors.lastname: Kisarova
authors.forename: Svetlana Ya
authors.initials: SY
authors.lastname: Zhanaeva
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Alexeenko
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Zhukova
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Brak
authors.forename: Victor K
authors.initials: VK
authors.lastname: Spiridonov
authors.forename: Elena E
authors.initials: EE
authors.lastname: Filjushina
authors.forename: Marina S
authors.initials: MS
authors.lastname: Cherkanova
authors.forename: Anna A
authors.initials: AA
authors.lastname: Monoszon
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002403:Cathepsins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000139:chemically induced* / Q000503:physiopathology; D005487:Foam Cells / Q000276:immunology / Q000648:ultrastructure; D006596:Hexosaminidases / Q000097:blood; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008074:Lipoproteins / Q000097:blood*; D053419:Lipoproteins, IDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000201:enzymology* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D020442:Poloxamer; D014280:Triglycerides / Q000097:blood
chemical_list: D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030104:lipoprotein cholesterol; C030087:lipoprotein triglyceride; D020442:Poloxamer; D002784:Cholesterol; D006596:Hexosaminidases; C086400:chitotriosidase; D002403:Cathepsins; D045726:Metalloproteases