Lovastatin inhibits low-density lipoprotein oxidation and alters its fluidity and uptake by macrophages: in vitro and in vivo studies
| Autor: | Uri Cogan, Michael Aviram, J.Gerald Brook, Edna Hochgraf, Gertrude Dankner |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
Antioxidant Endocrinology Diabetes and Metabolism medicine.medical_treatment Probucol Lipoproteins VLDL Hyperlipoproteinemia Type II chemistry.chemical_compound Mice Endocrinology Internal medicine medicine TBARS Animals Humans Lovastatin Cells Cultured Cholesterol Macrophages Biological Transport Malondialdehyde Lipoproteins LDL Kinetics chemistry Low-density lipoprotein lipids (amino acids peptides and proteins) Cholesterol Esters Lipoproteins HDL Diphenylhexatriene Oxidation-Reduction medicine.drug Lipoprotein |
| Zdroj: | Metabolism: clinical and experimental. 41(3) |
| ISSN: | 0026-0495 |
| Popis: | Under experimental conditions, oxidized low-density lipoprotein (Ox-LDL) may possess atherogenic properties, as is evidenced by its contribution to cholesterol accumulation in macrophages. LDL was oxidized in a cell-free system by predialysis of the lipoprotein against EDTA-free buffer and the addition of copper ions. Oxidation of LDL in the presence of lovastatin (10 to 1,000 mumol/L) resulted in a time- and dose-dependent reduction in thiobarbituric-acid-reactive substances (TBARS) concentration that was accompanied by increased LDL lysine-amino-group reactivity, in comparison with Ox-LDL produced in the absence of lovastatin. At 100 mumol/L, the drug reduced malondialdehyde concentration and increased amino-group reactivity by 24% and 42%, respectively. However, lovastatin's antioxidant effect was limited relative to other antioxidants, such as probucol and vitamin E. The fluidity of Ox-LDL was substantially reduced in comparison with native LDL. However, lovastatin inhibited this reduction in fluidity by 20%. Upon incubation of J-774 macrophage-like cell line with Ox-LDL, the lovastatin-treated Ox-LDL induced a reduction in the cellular cholesterol esterification rate in comparison with the effect of Ox-LDL that was produced in the absence of the drug. In four patients with hypercholesterolemia, the effect of lovastatin therapy (20 mg/d) on the sensitivity of their LDL to in vitro oxidation was studied. In all patients, Ox-LDL prepared from LDL obtained during lovastatin treatment demonstrated a reduced TBARS content, an increased trinitrobenzenesulfonic acid (TNBS) reactivity, an increased fluidity, and an impaired uptake by macrophages. These results were similar to those obtained by adding lovastatin in vitro. |
| Databáze: | OpenAIRE |
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