Effects of L-Carnitine on Propofol-Induced Inhibition of Free Fatty Acid Metabolism in Fasted Rats and in Vitro

摘要

Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose, and amino acid metabolism, as well as whether L-carnitine may improve suppression of free fatty acid metabolism. Methods: Male Sprague-Dawley rats, fasted for 16 hours, were allocated to the following two groups: (Group P;continuous intravenous administration of 10 mg/kg/h propofol;n = 8) and (Group P + C;intravenous administration of 50 mg/kg and then 50 mg/kg/h L-carnitine continuously;n = 8). Concentrations of glucose, free fatty acid (FFA), amino acids, in-sulin, and β-hydroxybutyric acid were measured at the start and then one, two, and three hours after propofol administration. Intrahepatic triglyceride levels were measured at the end of experiments. In vitro experiments comprised measurement of oxygen consumption in human hepatocytes (Hepg2) and investigating dependency on palmitic acid, glucose, and glutamine as fuel during propofol administration, with or without L-carnitine. Results: FFA increased in Group P and gradually decreased in Group P + C. There were significant differences between the two groups (Group P;331.2 ± 64.5 μM vs. Group P + C;199 ± 73.6 μM). Glucose decreased in both groups (Group P;53.8 ±16.6 mg/dL vs. Group P + C;88 ± 11.3 mg/dL). Amino acid concentrations were higher in Group P + C after experiments;alanine and glutamine increased significantly. β-hydroxybutyric acid increased significantly in Group P + C, and intrahepatic triglyceride decreased in Group P + C. Dependency on fatty acid metabolism significantly decreased with propofol only;addition of L-carnitine prevented these effects. Conclusions: Propofol impaired mitochondrial fatty acid metabolism, which was compensated mainly by a switch to glucose metabolism and partially by amino acid metabolism. Addition of L-carnitine may improve this imbalance of energy metabolism.