Propofol inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression through decreasing the generation of superoxide anion in cardiomyocytes

Jing Tang; Ji-Jie Hu; Chun-Hua Lu; Jia-Ni Liang; Jin-Fang Xiao; You-Tan Liu; Chun-Shui Lin; Zai-Sheng Qin

doi:10.1155/2014/157376

Propofol inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression through decreasing the generation of superoxide anion in cardiomyocytes

Oxid Med Cell Longev. 2014:2014:157376. doi: 10.1155/2014/157376. Epub 2014 Aug 11.

Authors

Jing Tang¹, Ji-Jie Hu², Chun-Hua Lu¹, Jia-Ni Liang¹, Jin-Fang Xiao¹, You-Tan Liu³, Chun-Shui Lin¹, Zai-Sheng Qin¹

Affiliations

¹ Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
² Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
³ Department of Anesthesiology, The University of Hongkong Shenzhen Hospital, Shenzhen, Guangdong 518053, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anesthetics, Intravenous / pharmacology*
Animals
Cell Survival / drug effects
Cells, Cultured
Depression / etiology
Depression / physiopathology
Endotoxemia / complications
Endotoxemia / mortality
Heart / drug effects
Heart / physiology
Lipopolysaccharides / toxicity
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / metabolism
Myocytes, Cardiac / cytology
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / metabolism
NADPH Oxidase 2
NADPH Oxidases / genetics
NADPH Oxidases / metabolism
Phosphorylation / drug effects
Propofol / pharmacology*
Signal Transduction / drug effects
Superoxides / metabolism*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism*

Substances

Anesthetics, Intravenous
Lipopolysaccharides
Membrane Glycoproteins
Tumor Necrosis Factor-alpha
Superoxides
Cybb protein, mouse
NADPH Oxidase 2
NADPH Oxidases
Mitogen-Activated Protein Kinases
Propofol