Dokument: Der Einfluss von Gemfibrozil und Pravastatin auf die mitochondriale Funktion im Colon und in der Leber in vitro - Ein Therapieansatz bei Sepsis?
| Titel: | Der Einfluss von Gemfibrozil und Pravastatin auf die mitochondriale Funktion im Colon und in der Leber in vitro - Ein Therapieansatz bei Sepsis? | |||||||
| Weiterer Titel: | Effect of Gemfibrozil and Pravastatin on hepatic and colonic mitochondrial function in vitro - A therapeutic option in sepsis? | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=55781 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210325-081847-6 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Laser, Eric [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Picker, Olaf [Gutachter] Dr. Flügen, Georg [Gutachter] | |||||||
| Stichwörter: | Mitochondrien, Sepsis, Colon, Leber, Gemfibrozil, Pravastatin | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Trotz großer Fortschritte in der Intensivmedizin stellen die Sepsis und der septische Schock, mit daraus resultierendem Multiorganversagen (MOF), weiterhin ein großes Problem mit enorm hoher Letalität der Patienten dar. Als eine wichtige Ursache des septischen Multiorganversagens werden eine Störung, sowohl der mitochondrialen Funktionen als auch der Mikrozirkulation, insbesondere im Gastrointestinaltrakt und der Leber, vermutet. In diesem Zusammenhang könnte der Einsatz von Statinen und Fibraten vielversprechend sein.
Um zu untersuchen, ob Gemfibrozil und Pravastatin die mitochondriale Funktion im Colon und in der Leber beeinflussen, wurden Gewebehomogenate aus Colon und Leber von gesunden Ratten mit verschiedenen Dosierungen dieser Medikamente inkubiert. Die mitochondriale Funktion wurde anschließend mittels Respirometrie beurteilt. In diesen Experimenten störte Gemfibrozil die hepatische ATP-Synthese durch Entkoppelung der Atmungskette. Pravastatin zeigte einen ähnlichen Effekt auf die ATP-Synthese, bewirkte aber keine Entkoppelung. Gemfibrozil senkte außerdem die Effizienz der oxidativen Phosphorylierung. Im Colon dagegen bewirkten beide Medikamente eher positive Effekte. Trotz Hemmung der Atmungskette kam es zu einer Stabilisierung des mitochondrialen Membranpotenzials. Zudem steigerten Gemfibrozil und Pravastatin die Effizienz der oxidativen Phosphorylierung. Diesen Ergebnissen zufolge beeinflussen Gemfibrozil und Pravastatin die mitochondriale Funktion im Colon und in der Leber auf unterschiedliche Weise. Ob dies tatsächlich einen positiven Einfluss auf das Outcome einer Sepsis haben könnte, muss durch Folgeversuche geklärt werden.Despite of many improvements in intensive care medicine sepsis, septic shock and septic multiorgan failure (MOF) remain a critical problem with high letality. Mitochondrial dysfunction and a impaired microcirculation, especially in the liver and the digestive system, are considered as important key factors in the developement of septic multi organ failure. In this context Statins and Fibrates might be an therapeutic option. In order to investigate the impact of Gemfibrozil and Pravastatin on hepatic and colonic mitochondrial function we incubated tissue homogenates from healthy rats with different dosages of these drugs. The mitochondrial function was measured via respirometry afterwards. Our study shows that hepatic ATP-synthesis is impaired by Gemfibrozil due to uncoupling. Pravastatin has an similiar effect but does not uncouple mitochondrial respiration from ATP-synthesis. The effects of both drugs on colonic mitochondria were rather positive. Despite of inhibiting mitochondrial respiration both drugs stabilized mitochondrial membrane potential. Furthermore both drugs improved the efficacy of oxidative phosphorylation. Our study shows that Gemfibrozil and Pravastatin impact hepatic and colonic mitochondrial function in different ways. It has to be investigated in future studies if this has a positive impact on sepsis. | |||||||
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2017 - 2021 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 25.03.2021 | |||||||
| Dateien geändert am: | 25.03.2021 | |||||||
| Promotionsantrag am: | 19.10.2020 | |||||||
| Datum der Promotion: | 11.03.2021 |
