Propofol affinity to mitochondrial membranes does not alter mitochondrial function.
The molecular mechanisms of hepatotoxicity after propofol anaesthesia have not been fully elucidated, although there is a relation with mitochondrial dysfunction. The action of propofol on mitochondrial hepatic functions in a rat model was evaluated by infusion for 4h with 25 and 62.5mg/kg/h propofol or 3.125ml/kg/h (vehicle). Liver mitochondrial respiratory rates were evaluated as well as mitochondrial transmembrane potential (ΔΨ), calcium fluxes, mitochondrial enzymatic activities (Complex I-V) and oxidative stress biomarkers (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, lipid peroxidation and the oxidised/reduced glutathione ratio). Biophysical interactions with membrane models were also performed. The mitochondrial transmembrane potential was decreased and the opening time of the mitochondrial permeability transition pore was slightly reduced for the highest dose. The activity of complex II was stimulated by propofol, which also causes fluctuations on some respiratory parameters, whereas the antioxidant system was affected in a nonspecific manner. Fluorescence quenching studies suggested that propofol is preferably located in deeper regions of the bilayer and has a high affinity to mitochondrial membranes. It is suggested that propofol interacts with liver mitochondrial membranes with mild modification in mitochondrial function.
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto (UP), Porto, Portugal. Electronic address: lfelix@utad.pt.
Luís M
LM
Félix
Chemistry Research Centre - Vila Real (CQ-VR), Chemistry Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Porto Hospital Center, Porto, Portugal.
Fernando
F
Correia
Chemistry Research Centre - Vila Real (CQ-VR), Chemistry Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
Pedro A
PA
Pinto
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Institute for Research and Innovation in Health (i3S), University of Porto (UP), Porto, Portugal.
Sónia P
SP
Campos
Chemistry Research Centre - Vila Real (CQ-VR), Chemistry Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
Telma
T
Fernandes
REQUIMTE/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto (UP), Porto, Portugal.
Romeu
R
Videira
Chemistry Research Centre - Vila Real (CQ-VR), Chemistry Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
M M
MM
Oliveira
Institute for Research and Innovation in Health (i3S), University of Porto (UP), Porto, Portugal.
Francisco P
FP
Peixoto
Institute for Research and Innovation in Health (i3S), University of Porto (UP), Porto, Portugal; Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
Luís M
LM
Antunes
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D015742:Propofol / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D015742:Propofol
Anaesthetic; Bioenergetics; Membrane partition; Mitochondria; Oxidative stress; Propofol