title: Propofol inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression through decreasing the generation of superoxide anion in cardiomyocytes.
abstract: TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis.
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Ji-Jie
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jia-Ni
authors.initials: JN
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, The University of Hongkong Shenzhen Hospital, Shenzhen, Guangdong 518053, China.
authors.forename: You-Tan
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Zai-Sheng
authors.initials: ZS
authors.lastname: Qin
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003863:Depression / Q000209:etiology / Q000503:physiopathology; D019446:Endotoxemia / Q000150:complications / Q000401:mortality; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; D015742:Propofol