Cytotoxicity caused by long-term propofol treatment in human induced pluripotent stem cell-derived cell lines

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20380
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ITO Hiroyuki 東京医科歯科大学, 医学部附属病院, 助教 (80595554)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: プロポフォール / 毒性 / ヒト人工多能性幹細胞 / 神経細胞

Outline of Final Research Achievements

Cultured human induced pluripotent stem (iPS) cell-derived neurons was used to study the toxic effects of propofol on human neurons. Human iPS cell-derived neural stem cells were cultured for 14 days and differentiated into neurons. These neurons were exposed to propofol for 48 hours. Propofol at 10μg/ml reduced NAD/NADH ratio by 24.6 %, cell viability by 12.3%, and caspase 3/7 activity was increased by 20.3%. Higher concentration of propofol (50μg/ml) caused further reduction in ATP level (17.9%), NAD/NADH ratio (40.1 %) and cell viability (15.9%), whereas augmentation in caspase 3/7 activity by 24.0%. Transmission electron microscopy showed autophagosomes, fragmentated mitochondria, and many vacuoles in the cytoplasm at 50μg/ml. Propofol dose-dependently reduced cell viability in cultured neuron at the range above clinical plasma concentration. Inhibitory effect on electron transport might reduce ATP production, which might result in the mitochondrial dysfunction.

Free Research Field

麻酔科学