Abstract
Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. In this work, human-induced pluripotent stem cell- (hiPSC-) derived neural progenitor cells (NPCs) were treated with propofol at 20, 50, 100, or 300 μM for 6 h or 24 h, and acute and subacute cell injury, cell proliferation, and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for treated and control iPSC-NPCs. Propofol treatment for 6 h at the clinically relevant concentration (20 or 50 μM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 μM) decreased NPC viability and induced apoptosis. In addition, 20 μM propofol treatment for 6 h did not alter global gene expression. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration could decrease NPC viability and induce apoptosis.
Highlights
Propofol (2,6-diisopropylphenol) is an anesthetic agent for induction and intravenous maintenance of anesthesia during surgery
neural progenitor cells (NPCs) treated with propofol at 20 or 50 μM for 6 h did not show any change in cell viability or late-stage cell injury as evaluated by MTT assay and Lactate Dehydrogenase (LDH) release (Figure 2), while NPCs treated with 300 μM propofol for 6 h showed significantly decreased cell viability (p < 0 01) and induced cytotoxicity in all three cell lines, especially in NPCs derived from ND2-0 Human-induced pluripotent stem cells (hiPSCs) line (Figure 2)
Propofol at 20 or 50 μM did not show any toxicity at 6 h, after 24 h of treatment, the 50 μM group showed a decrease in NPC viability in all cell lines (Figure 2), indicating that sustained exposure of propofol could result in negative effects on cell viability
Summary
Propofol (2,6-diisopropylphenol) is an anesthetic agent for induction and intravenous maintenance of anesthesia during surgery. Some reports have linked general anesthetic use in rodent and nonhuman primate babies with induced widespread neuronal degeneration and/or apoptosis followed by longterm memory and learning deficiency in adults [6,7,8,9,10,11,12,13,14], while other reports have suggested that no such association exists [15] These controversies could partly stem from the lack of recapitulative models that truly reflect the response of human brain cells to the treatment of general anesthetics agents including propofol
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