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Metabolic Effects of Propofol in the Isolated Perfused Rat Liver
Author(s) -
Acco Alexandra,
Comar Jurandir Fernando,
Bracht Adelar
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.pto950404.x
Subject(s) - gluconeogenesis , glycolysis , glycogenolysis , propofol , oxidative phosphorylation , metabolism , medicine , endocrinology , stimulation , oligomycin , chemistry , biochemistry , biology , pharmacology , enzyme , atpase
Inhibitory effects of the intravenous anaesthetic propofol on mitochondrial energy metabolism have been reported by several authors. Impairment of energy metabolism is usually coupled to reduction in ATP production, which in turn is expected to lead to several alterations in cell metabolism such as stimulation of glycolysis and inhibition of gluconeogenesis. The present work aimed at finding an answer to the question of how propofol affects energy metabolism‐linked parameters in the isolated perfused rat liver. In the fed state, propofol increased glycogenolysis (glucose release), glycolysis (lactate and pyruvate production) and oxygen uptake in the range between 10 and 500 μM. In the liver of fasted rats, propofol up to 100 μM increased oxygen uptake but decreased gluconeogenesis from three different substrates: lactate, alanine and glycerol. When lactate was the substrate 50% inhibition occurred at a propofol concentration of 50 μM. Propofol (100 μM) decreased the ATP content of the liver (−33.3%), increased the AMP content (+25%) and decreased the ATP/ADP and ATP/AMP ratios (49 and 45%, respectively). Most effects of propofol are probably due to impairment of oxidative phosphorylation. Particularly, the combined differential action on oxygen uptake (stimulation) and gluconeogenesis (inhibition) is strongly suggestive of an uncoupling action also under the conditions of the intact cell. This effect, in turn, is consistent with the reported high affinity of the cellular hepatic structure, especially membranes, for propofol.