OBJECTIVE: The aim of this study was to determine whether Microdispersed Oxidized Cellulose (MDOC) possesses a hypolipidemic effect in apolipoprotein-E/low-density lipoprotein receptor double-knockout (ApoE/LDLR-deficient) mice and the possible mechanism of this effect in mice. METHODS: Female ApoE/LDLR-deficient mice subdivided into two groups were fed with a Western-type diet for 8 wk, and the experimental group was supplemented with 5% MDOC for 8 wk. Female C57BL/6J mice were fed an atherogenic diet containing 5% MDOC or pectin for the determination of a possible hypolipidemic mechanism of MDOC action. RESULTS: Biochemical analysis showed that 5% MDOC treatment significantly decreased total cholesterol by 20% (P = 0.0338) and very-LDL cholesterol by 21% (P = 0.0110) and significantly increased the level of high-density lipoprotein cholesterol by 62% (P = 0.0172) when compared with non-treated ApoE/LDLR-deficient mice. The results Association of Official Analytical Chemists method 991.43 revealed that MDOC contains 59.78 +/- 5.0% of fiber. Furthermore, it was demonstrated that administration of MDOC did not affect cholesterol absorption in the small intestine. Using C57BL/6J mice, MDOC and pectin treatments decreased cholesterol content in liver and increased fermentation in the gut in vivo. In vitro experiments confirmed that MDOC is fermentable under conditions mimicking those in the large intestine. CONCLUSION: We demonstrated hypolipidemic effects of MDOC in ApoE/LDLR-deficient mice. Moreover, we propose that MDOC is a hypolipidemic soluble fiber acting probably by increased fermentation and production of short-chain fatty acids in the large intestine in mice. We propose that MDOC might be a possible source of soluble fiber for use in dietary supplements.
- MeSH
- apolipoproteiny E genetika nedostatek MeSH
- celulosa oxidovaná farmakologie MeSH
- cholesterol krev MeSH
- fermentace MeSH
- HDL-cholesterol krev MeSH
- hypolipidemika farmakologie MeSH
- intestinální absorpce fyziologie účinky léků MeSH
- kyseliny mastné těkavé analýza MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- náhodné rozdělení MeSH
- potravní vláknina aplikace a dávkování farmakologie MeSH
- receptory LDL genetika nedostatek MeSH
- tlusté střevo metabolismus MeSH
- VLDL-cholesterol krev MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- apolipoproteiny E krev metabolismus MeSH
- ateroskleróza * metabolismus prevence a kontrola MeSH
- azetidiny metabolismus terapeutické užití MeSH
- celulosa oxidovaná klasifikace terapeutické užití MeSH
- cholesterol klasifikace krev metabolismus MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- hyperlipidemie * metabolismus prevence a kontrola MeSH
- myši knockoutované MeSH
- pektiny metabolismus terapeutické užití MeSH
- potravní doplňky využití MeSH
- potravní vláknina * metabolismus terapeutické užití MeSH
- statiny metabolismus terapeutické užití MeSH
- statistika jako téma MeSH
- tlusté střevo metabolismus účinky léků MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherogenesis. The aim of this study was to detect and quantify the changes of endothelial expression of VCAM-1, and ICAM-1 in the vessel wall after the short-term administration of simvastatin, atorvastatin, and micro dispersed derivatives of oxidised cellulose (MDOC) in apolipoprotein-E-deficient (apoE(-/-)) mice atherosclerotic model. Hyperlipidemic apoE(-/-) mice (n = 32) received normal chow diet or diet containing simvastatin or atorvastatin 10 mg/kg/day or MDOC 50 mg/kg/day. Total cholesterol, VLDL, LDL, HDL and TAG were measured and the endothelial expression of VCAM-1 and ICAM-1 was visualized and quantified by means of immunohistochemistry and stereology, respectively. Total cholesterol levels was insignificantly lowered only in MDOC treated mice but not in mice treated with statins. ICAM-1 endothelial expression was not affected by neither simvastatin nor MDOC treatment. However, significant diminution of VCAM-1 endothelial expression was observed in both atorvastatin and MDOC treated mice. These results provide new information of potential hypolipidemic substance MDOC and its potential anti-inflammatory effects. Furthermore, we have confirmed anti-inflammatory effects of atorvastatin independent of plasma cholesterol lowering. Thus, the results of this study show potential benefit of both MDOC and atorvastatin treatment in apoE(-/-) mouse model of atherosclerosis suggesting their possible combination might be of interest.
- MeSH
- antiflogistika farmakologie terapeutické užití MeSH
- aplikace orální MeSH
- apolipoproteiny E genetika nedostatek MeSH
- ateroskleróza farmakoterapie MeSH
- celulosa oxidovaná farmakologie terapeutické užití MeSH
- cévní buněčněadhezivní molekula-1 metabolismus MeSH
- cévní endotel metabolismus patologie účinky léků MeSH
- dieta MeSH
- financování organizované MeSH
- hyperlipidemie farmakoterapie MeSH
- kyseliny heptylové farmakologie terapeutické užití MeSH
- lipoproteiny krev MeSH
- mezibuněčná adhezivní molekula-1 metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované MeSH
- myši MeSH
- pyrroly farmakologie terapeutické užití MeSH
- simvastatin farmakologie MeSH
- triglyceridy krev MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
