ABSTRACT
AIM: Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. METHODS: Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by ßVLDL derived from both groups of rabbits was also investigated. RESULTS: Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of ßVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with ßVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with ßVLDL from the control group. CONCLUSION: Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions.
Subject(s)
Atherosclerosis/prevention & control , Polysaccharides/pharmacology , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anticholesteremic Agents/pharmacology , Antioxidants/pharmacology , Aorta, Thoracic/pathology , Atherosclerosis/etiology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cell Line , Cholesterol/blood , Cholesterol/metabolism , Cholesterol, Dietary/administration & dosage , Diet, Atherogenic , Feces/chemistry , Galactose/metabolism , Lipid Peroxides/metabolism , Lipoproteins, IDL/metabolism , Lipoproteins, IDL/pharmacology , Liver/metabolism , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Polysaccharides/administration & dosage , RabbitsABSTRACT
OBJECTIVES: Pitavastatin is the first totally synthetic HMG-Co A reductase inhibitor in Japan that significantly reduces LDL cholesterol while raising HDL cholesterol. Clinical trial showed that pitavastatin has potent effects for LDL cholesterol lowering and is expected effectively to prevent atherosclerosis. To clarify the mechanism of reduction of atherosclerosis by pitavastatin, we examined the effect of pitavastatin on foam cell formation of RAW264.7 macrophages. METHODS & RESULTS: Macrophages were cultured with pitavastatin for 24 h and exposed to oxidized LDL with pitavastatin for 3 days. Pitavastatin decreased the cellular cholesteryl ester content in a dose-dependent manner, and this effect was not via inhibition of HMG-CoA reductase because the 3-30 nM pitavastatin did not inhibit [14C]cholesterol synthesis from [14C]acetic acid and the effect was not influenced by addition of mevalonic acid. Pitavastatin increased neutral cholesterol esterase (NCEase) activity and did not affect ACAT activity, and decreased the expression of CD36 and ABCA1 mRNA. The mechanism of the increase of NCEase activity was that pitavastatin directly modified the substrate state, which was cholesterol oleate emulsified with lecithin. CONCLUSION: Clinical blood concentrations of pitavastatin prevent foam cell formation of RAW macrophages by oxidized LDL, and this was not via inhibition of HMG-CoA reductase, and modify substrate condition.
