The Basic Study of the Mechanism of Propofol-Related Infusion Syndrome Using a Murine Skeletal Muscle Injury Model

Abstract

Background The pathophysiological mechanism of propofol-related infusion syndrome (PRIS) is believed to be due to the injury to the mitochondrial electron transport chain and the resultant metabolic disorders that are caused by both propofol agents and the lipid solvent. However, the mechanisms and causative factors of PRIS have not been fully elucidated. Objectives The aim of this study was to evaluate the possibility of a research model using the culture of differentiated C2C12 cells for fundamental research of PRIS. Methods First, differentiated C2C12 cells were cultured accompanied by several concentrations of chemical reagents of 2,6-diisopropylphenol (2,6 DIP) or dimethyl sulfoxide (DMSO) for 60 hours and the cell death rate was examined by trypan blue staining. Second, The cells were incubated with a commercially available propofol reagent or lipid reagent for 48 hours. The supernatant fluid of the cell culture medium was gathered and the numbers of floating cells were measured by cell counter. To investigate the mitochondrial disorder by the propofol preparation, JC-1, an experiment using fluorescent reagent, was performed for the 48 hours with 100 µg/mL propofol incubation. Results The rate of cell death was increased with elevating concentrations both of chemical reagents of 2,6 DIP group and dimethyl sulfoxide group. The rates of cell death were significantly higher in the 2,6 DIP group than DMSO group. The numbers of floating cells were increased with elevating concentrations both commercially available propofol reagent and lipid reagent groups. The decreased red/green fluorescence ratio by JC-1 staining in the propofol 100µg/mL group proved an attenuated mitochondrial membrane potential. Conclusions The dose-dependent cell damage induced by the propofol reagents and a lipid solvent may provide a proposed model as a basic experimental model for further investigations into PRIS.

Developing In Vitro Models to Define the Role of Direct Mitochondrial Toxicity in Frequently Reported Drug-Induced Rhabdomyolysis

“…Propofol has been shown to impair mitochondrial function via the inhibition of complex II + III activity in an in vivo rat model [69]. Moreover, propofol can inhibit fatty acid oxidation and the flux of electrons through the inner mitochondrial membrane, which is more pronounced in human than rat tissue [70] and can attenuate mitochondrial membrane potential in differentiated C2C12 cells [71]. In contrast, pregabalin has not previously been cited as causing mitochondrial dysfunction in vivo or in vitro skeletal muscle.…”

Ginsenoside Rg3 protects glucocorticoid‑induced muscle atrophy in vitro through improving mitochondrial biogenesis and myotube growth

“…In short, C2C12 myotubes were cultured in a 96-well plate under different treatment conditions, incubated for 30 min at 37°C using 10 µg/ml of JC-1 and analyzed thereafter using a fluorescence spectrometer (GloMax Discovery; Promega Corporation). The quantitative analysis was conducted using the fluorescence ration (590 to 530 nm) ( 22 ). The ATP Determination kit (Molecular Probes; Thermo Fisher Scientific, Inc.) was used to measure the total ATP content, as instructed by the manufacturer.…”

The Influence of Analgesic Modalities on Postoperative Cancer Recurrence

“…Propofol, an already widely used alternative to inhaled anesthetics, shows promise for preserving NK-cell cytotoxicity and suppressing the surgical stress response (64,65). It has been shown to suppress inflammatory cytokines and prostaglandins in several studies (66).…”