Ezetimibe reduces cholesterol content and NF-kappaB activation in liver but not in intestinal tissue in guinea pigs
| Autor: | Elisabeth F. Gröne, Heinz Drexel, Peter Fraunberger, Hermann Josef Gröne, Autar K. Walli |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Brush border Clinical Biochemistry Inflammation 030204 cardiovascular system & hematology Guinea pig 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ezetimibe Internal medicine medicine biology business.industry Cholesterol Research Fatty liver Cell Biology Hepatitis C medicine.disease Intestine 030104 developmental biology Endocrinology Liver chemistry HMG-CoA reductase Guinea pigs biology.protein lipids (amino acids peptides and proteins) medicine.symptom business medicine.drug |
| Zdroj: | Journal of Inflammation (London, England) |
| ISSN: | 1476-9255 |
| Popis: | Background Statins (HMG CoA reductase inhibitors), in addition to reducing circulating cholesterol and incidence of coronary heart disease, also have pleiotropic, anti-inflammatory effects. Patients with chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) or hepatitis C are often excluded from statin therapy because of adverse effects in a small cohort of patients despite increased cardiovascular risk cholesterol. Ezetimibe, which inhibits cholesterol absorption by inhibition of Niemann-Pick C1 like 1 (NPC1L1) protein in the brush border of intestinal cells, has been suggested as a new therapeutic option in these patients. Methods Effects of ezetimibe on lipoprotein metabolism, hepatic and intestinal lipid content in guinea pigs, an animal model with a lipoprotein profile and pattern similar to humans were investigated. In order to investigate a possible effect of ezetimibe on cholesterol induced inflammation NF-kappaB activation as an indicator for inflammatory processes in liver and gut tissue was measured. Results Lipid enriched diet led to accumulation of lipids in hepatic tissue which caused strong hepatic NF-kappaB activation. Ezetimibe reduced lipid diet induced increase of circulating cholesterol by about 77% and prevent hepatic NF-kappaB activation almost completely. In contrast in intestinal cells Ezetimibe, though lowering diet induced cholesterol accumulation, increased triglyceride content and subsequent NF-kappaB activation. Conclusion In summary these data show, that ezetimibe effectively reduced diet induced circulating cholesterol levels, hepatic lipid accumulation and inflammatory response in our guinea pig model. However this drug elicited a local inflammatory response in intestinal tissue. Whether these diverse effects of ezetimibe on inflammatory parameters such as NF-kappaB have clinical relevance remains to be determined. |
| Databáze: | OpenAIRE |
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