Abstract
Nitric oxide is an active oxidant that contributes to the physiology and pathophysiology of macrophages. Propofol has been widely used in intravenous anesthesia. It possess antioxidant and immunomodulating effects. This study aimed to evaluate the effects of propofol on nitric oxide production in lipopolysaccharide-activated macrophages. Exposure of macrophages to propofol (25, 50 and 75 µM), to lipopolysaccharide (0.5, 1, 1.5 and 2 ng/ml) or to a combination of propofol and lipopolysaccharide did not affect cell viability. However, propofol at 100 µM led to significant cell death (P<0.05). The levels of nitrite, an oxidative product of nitric oxide, were increased in lipopolysaccharide-treated macrophages in a concentration-dependent manner (P<0.01), while propofol could concentration-dependently decrease the lipopolysaccharide-enhanced nitrite levels (P<0.01). Immunoblotting analysis revealed that lipopolysaccharide increased the protein level of inducible nitric oxide synthase (iNOS). The co-treatment of propofol and lipopolysaccharide significantly reduced this lipopolysaccharide-induced iNOS protein (357±49×103 versus 92±6×103 arbitrary units, P<0.01). Analysis by reverse transcriptase-polymerase chain reaction showed that lipopolysaccharide induced mRNA of iNOS, but that the inductive effect was inhibited by propofol (95±7×102 versus 30±4×102 arbitrary units, P<0.01). This study has demonstrated that propofol, at therapeutic concentrations, could suppress nitric oxide biosynthesis by inhibiting iNOS expression in lipopolysaccharide-activated macrophages. The mechanism of suppression was at a pretranslational level.
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Acknowledgements
The authors express their gratitude to Ms Sheau-Lan Tzeng and Ms Wan-Ju Lee for their technical support and data collection of the experiment. This study is supported by grants TMU90-Y05-A123 from Taipei Medical University and NSC90-2314-B-038-045 from the National Science Council, Taiwan, ROC.
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Chen, RM., Wu, GJ., Tai, YT. et al. Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase. Arch Toxicol 77, 418–423 (2003). https://doi.org/10.1007/s00204-003-0453-z
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DOI: https://doi.org/10.1007/s00204-003-0453-z