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Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats

Statins and fibrates are widely used for the management of hypertriglyceridemia but they also have limitations, mostly due to pharmacokinetic interactions or side effects. It is conceivable that some adverse events like liver dysfunction or gastrointestinal discomfort are caused by mitochondrial dys...

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Autores principales: Herminghaus, Anna, Laser, Eric, Schulz, Jan, Truse, Richard, Vollmer, Christian, Bauer, Inge, Picker, Olaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769625/
https://www.ncbi.nlm.nih.gov/pubmed/31461874
http://dx.doi.org/10.3390/cells8090983
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author Herminghaus, Anna
Laser, Eric
Schulz, Jan
Truse, Richard
Vollmer, Christian
Bauer, Inge
Picker, Olaf
author_facet Herminghaus, Anna
Laser, Eric
Schulz, Jan
Truse, Richard
Vollmer, Christian
Bauer, Inge
Picker, Olaf
author_sort Herminghaus, Anna
collection PubMed
description Statins and fibrates are widely used for the management of hypertriglyceridemia but they also have limitations, mostly due to pharmacokinetic interactions or side effects. It is conceivable that some adverse events like liver dysfunction or gastrointestinal discomfort are caused by mitochondrial dysfunction. Data about the effects of statins and fibrates on mitochondrial function in different organs are inconsistent and partially contradictory. The aim of this study was to investigate the effect of pravastatin (statin) and gemfibrozil (fibrate) on hepatic and colonic mitochondrial respiration in tissue homogenates. Mitochondrial oxygen consumption was determined in colon and liver homogenates from 48 healthy rats after incubation with pravastatin or gemfibrozil (100, 300, 1000 μM). State 2 (substrate dependent respiration) and state 3 (adenosine diphosphate: ADP-dependent respiration) were assessed. RCI (respiratory control index)—an indicator for coupling between electron transport chain system (ETS) and oxidative phosphorylation (OXPHOS) and ADP/O ratio—a parameter for the efficacy of OXPHOS, was calculated. Data were presented as a percentage of control (Kruskal–Wallis + Dunn’s correction). In the liver both drugs reduced state 3 and RCI, gemfibrozil-reduced ADP/O (complex I). In the colon both drugs reduced state 3 but enhanced ADP/O. Pravastatin at high concentration (1000 µM) decreased RCI (complex II). Pravastatin and gemfibrozil decrease hepatic but increase colonic mitochondrial respiration in tissue homogenates from healthy rats.
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spelling pubmed-67696252019-10-30 Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats Herminghaus, Anna Laser, Eric Schulz, Jan Truse, Richard Vollmer, Christian Bauer, Inge Picker, Olaf Cells Article Statins and fibrates are widely used for the management of hypertriglyceridemia but they also have limitations, mostly due to pharmacokinetic interactions or side effects. It is conceivable that some adverse events like liver dysfunction or gastrointestinal discomfort are caused by mitochondrial dysfunction. Data about the effects of statins and fibrates on mitochondrial function in different organs are inconsistent and partially contradictory. The aim of this study was to investigate the effect of pravastatin (statin) and gemfibrozil (fibrate) on hepatic and colonic mitochondrial respiration in tissue homogenates. Mitochondrial oxygen consumption was determined in colon and liver homogenates from 48 healthy rats after incubation with pravastatin or gemfibrozil (100, 300, 1000 μM). State 2 (substrate dependent respiration) and state 3 (adenosine diphosphate: ADP-dependent respiration) were assessed. RCI (respiratory control index)—an indicator for coupling between electron transport chain system (ETS) and oxidative phosphorylation (OXPHOS) and ADP/O ratio—a parameter for the efficacy of OXPHOS, was calculated. Data were presented as a percentage of control (Kruskal–Wallis + Dunn’s correction). In the liver both drugs reduced state 3 and RCI, gemfibrozil-reduced ADP/O (complex I). In the colon both drugs reduced state 3 but enhanced ADP/O. Pravastatin at high concentration (1000 µM) decreased RCI (complex II). Pravastatin and gemfibrozil decrease hepatic but increase colonic mitochondrial respiration in tissue homogenates from healthy rats. MDPI 2019-08-27 /pmc/articles/PMC6769625/ /pubmed/31461874 http://dx.doi.org/10.3390/cells8090983 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herminghaus, Anna
Laser, Eric
Schulz, Jan
Truse, Richard
Vollmer, Christian
Bauer, Inge
Picker, Olaf
Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title_full Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title_fullStr Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title_full_unstemmed Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title_short Pravastatin and Gemfibrozil Modulate Differently Hepatic and Colonic Mitochondrial Respiration in Tissue Homogenates from Healthy Rats
title_sort pravastatin and gemfibrozil modulate differently hepatic and colonic mitochondrial respiration in tissue homogenates from healthy rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769625/
https://www.ncbi.nlm.nih.gov/pubmed/31461874
http://dx.doi.org/10.3390/cells8090983
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