Influence of atorvastatin on fractional and subfractional composition of serum lipoproteins and MMP activity in mice with Triton WR 1339-induced lipaemia

Autor: V. I. Kaledin, Thomas P. Johnston, Natalia A. Tuzikova, Marina S. Cherkanova, Viktoriya M. Loginova, Tatyana A. Korolenko, F. V. Tuzikov
Rok vydání: 2011
Předmět:
Zdroj: Journal of Pharmacy and Pharmacology. 63:833-839
ISSN: 2042-7158
0022-3573
DOI: 10.1111/j.2042-7158.2011.01287.x
Popis: Objectives The effects of atorvastatin on the atherogenic and anti-atherogenic lipoprotein-cholesterol (C-LP) and lipoprotein-triglyceride (TG-LP) fractions and subfractions at the early stage of murine acute hyperlipidaemia, and its pleiotropic anti-inflammatory effects via the activity of matrix metalloproteinases (MMPs) were studied. Methods Atorvastatin (75 mg/kg) was administered to ICR mice with acute lipaemia induced by a single injection of Triton WR 1339 (500 mg/kg). A novel small-angle X-ray scattering (SAXS) method was used for the determination of the fractional and subfractional composition of C-LP and TG-LP. Key finding In Triton WR 1339-treated mice, there was a drastic increase in the atherogenic low-density C-LP (C-LDL) fraction, intermediate density lipoprotein-cholesterol (C-IDL) subfraction, and very low-density C-LP (C-VLDL) fractions (C-VLDL3–5 subfraction). Additionally, there was an increase in the C-HDL3 subfraction. Treatment of lipaemia with atorvastatin resulted in the normalization of the atherogenic C-LDL fraction and the C-IDL subfraction. A decrease in C-VLDL (C-VLDL3–5 subfraction), total cholesterol and, especially, triglyceride (TG) concentrations was also demonstrated. Similar results were obtained with the TG-LP fractions and subfractions. Additionally, atorvastatin treatment resulted in an increase in the serum and liver MMP activity. Conclusion High-dose atorvastatin therapy exerts its rapid lipid-lowering and pleiotropic effect(s) in the early stages of acute lipaemia induced with Triton WR-1339.
Databáze: OpenAIRE