Influence of atorvastatin and carboxymethylated glucan on the serum lipoprotein profile and MMP activity of mice with lipemia induced by poloxamer 407.
The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407-treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL(1-3)-C subfractions) and very low-density lipoprotein-C (VLDL-C) (VLDL(1-2)-C and VLDL(3-5)-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL(2)-C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL(1-3)-C subfraction), and the LDL(1-3)-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P-407.
Institute of Physiology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Timakov Street 4, 630117, Russia. t.a.korolenko@physiol.ru
Tatyana A
TA
Korolenko
Fedor V
FV
Tuzikov
Marina S
MS
Cherkanova
Thomas P
TP
Johnston
Natalia A
NA
Tuzikova
Viktoriya M
VM
Loginova
Elena E
EE
Filjushina
Vassilij I
VI
Kaledin
D000818:Animals; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D051379:Mice; D008813:Mice, Inbred ICR; D020442:Poloxamer; D011758:Pyrroles / Q000494:pharmacology*; D053838:Scattering, Small Angle; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014961:X-Ray Diffraction; D047071:beta-Glucans / Q000494:pharmacology*
D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014280:Triglycerides; D047071:beta-Glucans; C032607:low density lipoprotein triglyceride; D020442:Poloxamer; C029933:carboxymethyl-beta-1,3-glucan; D000069059:Atorvastatin; D020782:Matrix Metalloproteinases