title: In vivo study of hepatic oxidative stress and mitochondrial function in rabbits with severe hypotension after propofol prolonged infusion.
abstract: In humans, prolonged sedations with propofol or using high doses have been associated with propofol infusion syndrome. The main objective of this study was to evaluate the effects of prolonged high-dose administration of a specific propofol emulsion (Propofol Lipuro) and an improved lipid formulation (SMOFlipid) in liver mitochondrial bioenergetics and oxidative stress of rabbits, comparatively to a saline control. Twenty-one male New Zealand white rabbits were randomly allocated in three groups that were continuously treated for 20 h. Each group of seven animals received separately: NaCl 0.9 % (saline), SMOFlipid (lipid-based emulsion without propofol) and Lipuro 2 % (propofol lipid emulsion). An intravenous propofol bolus of 20 mg kg(-1) was given to the propofol Lipuro group to allow blind orotracheal intubation and mechanical ventilation. Anesthesia was maintained using infusion rates of: 20, 30, 40, 50 and 60 mg kg(-1) h(-1), according to the clinical scale of anesthetic depth and the index of consciousness values. The SMOFlipid and saline groups received the same infusion rate as the propofol Lipuro group, which were infused during 20 consecutive hours. At the end, the animals were euthanized, livers collected and mitochondria isolated by standard differential centrifugation. Mitochondrial respiration, membrane potential, swelling and oxidative stress were evaluated. Data were processed using one-way ANOVA (p < 0.05). The animals revealed a significant decrease in cardiovascular parameters showing bradycardia and severe hypotension. No statistical differences were observed when using pyruvate as substrate, however, when using succinate as respiratory substrate, significant decrease in ADP-stimulated respiration rate was observed for SMOFlipid group (p = 0.002). Lipid peroxides (p < 0.01) and protein carbonyls (p = 0.01) showed a statistically significant difference between propofol Lipuro and the SMOFlipid groups. These results suggest that lipid-based emulsions can be involved in the regulation of different pathways that ultimately lead to a decrease of state 3 mitochondrial respiration rate. The infusion of propofol Lipuro during prolonged periods, in addition to marked hypotension and hypoperfusion, also showed to have higher anti-oxidant activity and lower impairment of the mitochondrial function comparatively to the improved lipid formulation, SMOFlipid, using the rabbit as animal model.
authors: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Apartado 1013, 5001-801 Vila Real, Portugal ; Institute for Research and Innovation in Health (i3S), Laboratory Animal Science, Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal ; UCIBIO@REQUIMTE-Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors: Sónia
authors: S
authors: Campos
authors: Institute for Research and Innovation in Health (i3S), Laboratory Animal Science, Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal ; Life Sciences and Environment School (ECVA), Department of Chemistry, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors: Luís
authors: L
authors: Félix
authors: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Apartado 1013, 5001-801 Vila Real, Portugal.
authors: Carlos
authors: C
authors: Venâncio
authors: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Apartado 1013, 5001-801 Vila Real, Portugal.
authors: Maria
authors: M
authors: de Lurdes Pinto
authors: Life Sciences and Environment School (ECVA), Department of Chemistry, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors: Francisco
authors: F
authors: Peixoto
authors: UCIBIO@REQUIMTE-Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors: Paula Guedes
authors: PG
authors: de Pinho
authors: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Apartado 1013, 5001-801 Vila Real, Portugal ; Institute for Research and Innovation in Health (i3S), Laboratory Animal Science, Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
authors: Luís
authors: L
authors: Antunes
keywords: Mitochondrial bioenergetics; Propofol; Propofol infusion syndrome (PRIS); Rabbit anesthesia