Journal du métabolisme des médicaments et de la toxicologie
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A Mechanism by Which Propofol Induces Cytotoxicity

Shin Onizuka, Nobunao Ikewaki and Seiji Shiraishi

Background: Many studies have reported on the cytotoxicity of propofol; however, the mechanism is still unclear. The aim of this study was to clarify the mechanisms of cytotoxicity induced by propofol.
Methods: Using Hela cells, viability was measured using a calcein-AM assay. Apoptosis was observed by DNA fragmentation, caspase activity. Mitochondrial membrane potential, and mitochondrial pH were measured using the ratiometric fluorescent probes JC-1 and SNARF-1 to clarify the mechanisms of mitochondrial cytotoxicity.
Furthermore, the pH of both the intra- and extra-membrane was measured simultaneously using 5-hexadecanoylaminofluorescein (HAF), a ratiometric pH sensitive fluorescent probe.
Results: Propofol (0~69.6 μM) reduced the viability of Hela cells in a dose- and time-dependent manner. Propofol induced apoptosis through the mitochondrial pathway, induced mitochondrial depolarization. Propofol (10 μM) also resulted in the loss of the pH gradient at cytosol and mitochondria, as did CCCP (10 μM).
Conclusion: Propofol acts as a protonophore, and this chemical property induces apoptosis in cancer cell lines through the mitochondrial pathway by disappearance of the pH gradient.