1. Propofol improves colonic but impairs hepatic mitochondrial function in tissue homogenates from healthy rats.
- Author
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Herminghaus A, Buitenhuis AJ, Schulz J, Vollmer C, Scheeren TWL, Bauer I, Picker O, and Truse R
- Subjects
- Animals, Cell Respiration drug effects, Dose-Response Relationship, Drug, Male, Organ Specificity, Oxidative Phosphorylation drug effects, Oxygen Consumption drug effects, Rats, Rats, Wistar, Colon cytology, Liver cytology, Mitochondria drug effects, Mitochondria metabolism, Propofol pharmacology
- Abstract
Evidence suggests that propofol infusion syndrome (PRIS) is caused by an altered mitochondrial function. The aim of this study was to examine the effects of propofol and the vehicle MCT on mitochondrial function in hepatic and colonic tissue. Mitochondrial oxygen consumption was determined in colon and liver homogenates after incubation with buffer (control), propofol (50, 75, 100, 500 μM) or the carrier substances DMSO and MCT. State 2 (substrate-dependent) and state 3 (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 efficacy of OXPHOS were calculated. Data were presented as % of control. In hepatic mitochondria, 500 μM propofol reduced RCI formulation-independently (propofol/MCT 500 μM: complex I: 66.3 ± 8.7%*, complex II: 75.5 ± 9.2%*; propofol/DMSO 500 μM: complex I: 29.1 ± 8.8%*, complex II: 49.3 ± 15.5%*). 75 μM Propofol/MCT reduced ADP/O for complex I (73.5 ± 27.3%*). DMSO did not affect hepatic mitochondria whereas MCT reduced RCI for complex II (87.2 ± 9.8%*) and ADP/O for complex I (93.7 ± 31.7%*). In colon 50 μM Propofol/MCT increased RCI for complex I and II (complex I: 127.2 ± 10.7%*, complex II: 136.8 ± 33.9%*) and 100 μM Propofol/MCT for complex I (131.4 ± 18.7%*). 500 μM Propofol/DMSO increased ADP/O for complex I (139.4 ± 41.4%*). DMSO did not affect RCI but increased ADP/O for both complexes (complex I: 119.9 ± 25.8%*, complex II: 110.2 ± 14.2%*). MCT increased RCI for complex I (123.0 ± 31.6%*). In hepatic mitochondria propofol uncoupled ETS from OXPHOS formulation-independently and propofol/MCT reduced efficacy of OXPHOS. In colonic mitochondria, propofol/MCT strengthened the coupling and propofol/DMSO enhanced the efficacy of OXPHOS., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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