A Mechanism by Which Propofol Induces Cytotoxicity

Onizuka, Shin; Ikewaki, Nobunao; Shiraishi, Seiji

doi:10.4172/2157-7609.1000230

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…This is consistent with the publications that demonstrated high cytotoxicity of propofol in various cell lines [ 37 , 38 ]. According to a recent publication, propofol acts as a classical protonophore, whereby the cytotoxicity could be based on the translocation of protons through double lipid layers [ 39 ]. Mitochondrial depolarisation would induce apoptosis through the activation of caspase-9, caspase-3, and DNA fragmentation [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…According to a recent publication, propofol acts as a classical protonophore, whereby the cytotoxicity could be based on the translocation of protons through double lipid layers [ 39 ]. Mitochondrial depolarisation would induce apoptosis through the activation of caspase-9, caspase-3, and DNA fragmentation [ 39 ]. The extent to which this mechanism can be confirmed has not yet been conclusively clarified.…”

Section: Resultsmentioning

confidence: 99%

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Chemical Analysis and Molecular Modelling of Cyclodextrin-Formulated Propofol and Its Sodium Salt to Improve Drug Solubility, Stability and Pharmacokinetics (Cytogenotoxicity)

2023

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Propofol is a widely used general anesthetic in clinical practice, but its use is limited by its water-insoluble nature and associated pharmacokinetic and pharmacodynamic limitations. Therefore, researchers have been searching for alternative formulations to lipid emulsion to address the remaining side effects. In this study, novel formulations for propofol and its sodium salt Na-propofolat were designed and tested using the amphiphilic cyclodextrin (CD) derivative hydroxypropyl-β-cyclodextrin (HPβCD). The study found that spectroscopic and calorimetric measurements suggested complex formation between propofol/Na-propofolate and HPβCD, which was confirmed by the absence of an evaporation peak and different glass transition temperatures. Moreover, the formulated compounds showed no cytotoxicity and genotoxicity compared to the reference. The molecular modeling simulations based on molecular docking predicted a higher affinity for propofol/HPβCD than for Na-propofolate/HPβCD, as the former complex was more stable. This finding was further confirmed by high-performance liquid chromatography. In conclusion, the CD-based formulations of propofol and its sodium salt may be a promising option and a plausible alternative to conventional lipid emulsions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%