Dokument: Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats

Titel:	Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68706
URN (NBN):	urn:nbn:de:hbz:061-20250219-111836-2
Kollektion:	Publikationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Texte » Artikel, Aufsatz
Medientyp:	Text
Autoren:	Kuebart, Anne [Autor] Gross, Katharina [Autor] Ripkens, Jan-Joschua [Autor] Tenge, Theresa [Autor] Raupach, Annika [Autor] Schulz, Jan [Autor] Truse, Richard [Autor] Hof, Stefan [Autor] Marcus, Carsten [Autor] Vollmer, Christian [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 699,5 KB in einer Datei [ZIP-Datei erzeugen] Dateien vom 19.02.2025 / geändert 19.02.2025
Stichwörter:	mitochondrial function, pravastatin, microcirculation, sepsis
Beschreibung:	Microcirculatory and mitochondrial dysfunction are considered the main mechanisms of septic shock. Studies suggest that statins modulate inflammatory response, microcirculation, and mitochondrial function, possibly through their action on peroxisome proliferator-activated receptor alpha (PPAR-α). The aim of this study was to examine the effects of pravastatin on microcirculation and mitochondrial function in the liver and colon and the role of PPAR-α under septic conditions. This study was performed with the approval of the local animal care and use committee. Forty Wistar rats were randomly divided into 4 groups: sepsis (colon ascendens stent peritonitis, CASP) without treatment as control, sepsis + pravastatin, sepsis + PPAR-α-blocker GW6471, and sepsis + pravastatin + GW6471. Pravastatin (200 µg/kg s.c.) and GW6471 (1 mg/kg) were applied 18 h before CASP-operation. 24 h after initial surgery, a relaparotomy was performed, followed by a 90 min observation period for assessment of microcirculatory oxygenation (μHbO2) of the liver and colon. At the end of the experiments, animals were euthanized, and the colon and liver were harvested. Mitochondrial function was measured in tissue homogenates using oximetry. The ADP/O ratio and respiratory control index (RCI) for complexes I and II were calculated. Reactive oxygen species (ROS) production was assessed using the malondialdehyde (MDA)-Assay. Statistics: two-way analysis of variance (ANOVA) + Tukey’s/Dunnett’s post hoc test for microcirculatory data, Kruskal–Wallis test + Dunn’s post hoc test for all other data. In control septic animals µHbO2 in liver and colon deteriorated over time (µHbO2: −9.8 ± 7.5%* and −7.6 ± 3.3%* vs. baseline, respectively), whereas after pravastatin and pravastatin + GW6471 treatment μHbO2 remained constant (liver: µHbO2 pravastatin: −4.21 ± 11.7%, pravastatin + GW6471: −0.08 ± 10.3%; colon: µHbO2 pravastatin: −0.13 ± 7.6%, pravastatin + GW6471: −3.00 ± 11.24%). In both organs, RCI and ADP/O were similar across all groups. The MDA concentration remained unchanged in all groups. Therefore, we conclude that under septic conditions pravastatin improves microcirculation in the colon and liver, and this seems independent of PPAR-α and without affecting mitochondrial function.
Rechtliche Vermerke:	Originalveröffentlichung: Kuebart, A., Gross, K., Ripkens, J.-J., Tenge, T., Raupach, A., Schulz, J. W., Truse, R., Hof, S., Marcus, C., Vollmer, C., Bauer, I., Picker, O., & Herminghaus, A. (2023). Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats. International Journal of Molecular Sciences, 24(6), Article 5455. https://doi.org/10.3390/ijms24065455
Lizenz:	Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:	Medizinische Fakultät
Dokument erstellt am:	19.02.2025
Dateien geändert am:	19.02.2025