Propofol improves colonic but impairs hepatic mitochondrial function in tissue homogenates from healthy rats

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.