Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α /HO-1 Pathway

Oxidative Medicine and Cellular Longevity
Chao HeFeng Xiao

Abstract

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. How...Continue Reading

References

Nov 15, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·L E Otterbein, A M Choi
Jun 5, 2003·Intensive Care Medicine·Cristiane RitterFelipe Dal-Pizzol
Sep 5, 2003·The Journal of Pharmacology and Experimental Therapeutics·Hiroshi KonoYoshiro Matsumoto
Jan 11, 2005·Lancet·Djillali AnnaneJean-Marc Cavaillon
Apr 5, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Ramzi OckailiRakesh C Kukreja
Apr 12, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Saadet TurksevenNader G Abraham
Jul 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Buddhadeb Dawn, Roberto Bolli
Oct 14, 2006·Nature Reviews. Immunology·Richard S Hotchkiss, Donald W Nicholson
Nov 4, 2006·Biological Chemistry·Jacques Pouysségur, Fatima Mechta-Grigoriou
Feb 3, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Steve BonelloAgnes Görlach
Apr 17, 2007·Molecular Cell·Fang LiChuan-Yuan Li
Apr 25, 2007·Critical Care Medicine·Alain Rudiger, Mervyn Singer
Nov 14, 2007·Methods in Enzymology·Agnes Görlach, Thomas Kietzmann
Nov 21, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ralph V Shohet, Joseph A Garcia
Sep 13, 2008·Current Opinion in Critical Care·Eirini Christaki, Steven M Opal
Nov 27, 2009·British Journal of Anaesthesia·J D Hunter, M Doddi
Feb 24, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Elina Pathak, Philip R Mayeux
Mar 19, 2011·The Tohoku Journal of Experimental Medicine·Sachiko YamaguchiHajime Togari
May 24, 2011·International Journal of Nephrology·C ChelazziA R De Gaudio
Oct 7, 2011·The Open Inflammation Journal·Derek S Wheeler
Jul 25, 2013·International Journal of Molecular Sciences·Kiyoshi KikuchiEiichiro Tanaka
Aug 30, 2013·The New England Journal of Medicine·Derek C Angus, Tom van der Poll
Jul 10, 2014·The American Journal of Chinese Medicine·Huai-Min ChenJwu-Lai Yeh
Apr 4, 2015·Journal of Pharmacological Sciences·Noriko NakajimaHiroaki Araki
May 3, 2016·Journal of Intensive and Critical Care·Brittany A PotzM Ruhul Abid
Sep 7, 2016·The International Journal of Biochemistry & Cell Biology·Juana P Sánchez-VillamilMaría C Carreras
Oct 7, 2016·Military Medical Research·Xiuxiu Lv, Huadong Wang
Jan 18, 2017·Journal of Anaesthesiology, Clinical Pharmacology·Ghada Fouad ElbaradeyHossam Hodeib
Aug 29, 2017·Oxidative Medicine and Cellular Longevity·Shiyan PengFeng Xiao

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Citations

Jan 24, 2020·The FEBS Journal·Tineke VanderhaeghenClaude Libert
Sep 27, 2019·Frontiers in Molecular Biosciences·Susan F Fitzpatrick
Nov 30, 2021·Molecular Medicine Reports·Lin-Lin MaYue-Ling Jin

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Methods Mentioned

BETA
Assay
ELISA
protein assay
MDA

Software Mentioned

GraphPad Prism
[UNK] TL
Image
Pro Plus

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