Extracellular nucleic acid scavenging rescues rats from sulfur mustard analog-induced lung injury and mortality.

Archives of Toxicology
Nithya MariappanAftab Ahmad

Abstract

Sulfur mustard (SM) is a highly toxic war chemical that causes significant morbidity and mortality and lacks any effective therapy. Rats exposed to aerosolized CEES (2-chloroethyl ethyl sulfide; 10% in ethanol), an analog of SM, developed acute respiratory distress syndrome (ARDS), which is characterized by increased inflammation, hypoxemia and impaired gas exchange. We observed elevated levels of extracellular nucleic acids (eNA) in the bronchoalveolar lavage fluid (BALF) of CEES-exposed animals. eNA can induce inflammation, coagulation and barrier dysfunction. Treatment with hexadimethrine bromide (HDMBr; 10 mg/kg), an eNA neutralizing agent, 2 h post-exposure, reduced lung injury, inhibited disruption of alveolar-capillary barrier, improved blood oxygenation (PaO2/FiO2 ratio), thus reversing ARDS symptoms. HDMBr treatment also reduced lung inflammation in the CEES-exposed animals by decreasing IL-6, IL-1A, CXCL-1 and CCL-2 mRNA levels in lung tissues and HMGB1 protein in BALF. Furthermore, HDMBr treatment also reduced levels of lung tissue factor and plasminogen activator inhibitor-1 indicating reduction in clot formation and increased fibrinolysis. Fibrin was reduced in BALF of the HDMBr-treated animals. This was further co...Continue Reading

References

Apr 1, 1992·Cell Biology and Toxicology·M ChevillardE Puchelle
Sep 1, 1994·Microvascular Research·J S ErjefältC G Persson
Feb 1, 1994·Journal of Applied Physiology·J H CalvetI Macquin-Mavier
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E AbrahamK J Tracey
Sep 5, 2002·Journal of Applied Toxicology : JAT·Shannon D McClintockPeter A Ward
Apr 12, 2003·Critical Care Medicine·Steven Idell
Apr 17, 2003·Journal of Endotoxin Research·Huan YangKevin J Tracey
Jun 20, 2003·Journal of Biochemical and Molecular Toxicology·Salil K DasDiptendu Chatterjee
Aug 23, 2003·Arthritis Research & Therapy·Shahin HajizadehL Vincent Collins
Aug 28, 2003·Current Opinion in Chemical Biology·Jeffrey A Lawton, Partho Ghosh
Sep 26, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gabriella SozziUgo Pastorino
Jan 5, 2005·Toxicology and Applied Pharmacology·R VijayaraghavanK Ganesan
Aug 9, 2005·Toxicology·Kai Kehe, Ladislaus Szinicz
Oct 28, 2005·Journal of Applied Toxicology : JAT·Shannon D McClintockPeter A Ward
May 27, 2006·American Journal of Respiratory and Critical Care Medicine·Eileen N OgawaJunzo Takeda
Oct 17, 2006·Basic & Clinical Pharmacology & Toxicology·Mahdi Balali-Mood, Mehrdad Hefazi
May 29, 2007·Burns : Journal of the International Society for Burn Injuries·Guang-Qing Wang, Zhao-Fan Xia
Jun 19, 2007·Chest·Todd W RiceUNKNOWN National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network
Aug 7, 1948·British Medical Journal·D C SINCLAIR
Jun 2, 2009·Toxicology·K KeheT Zilker
Jul 20, 2010·American Journal of Respiratory and Critical Care Medicine·Livia A VeressCarl W White
Sep 21, 2010·Pulmonary Pharmacology & Therapeutics·Barry WeinbergerDebra L Laskin
Nov 3, 2010·International Journal of Chronic Obstructive Pulmonary Disease·Davood AttaranReza Basiri
Dec 15, 2010·Microvascular Research·Rachel K WolfsonJoe G N Garcia
Aug 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jaewoo LeeBruce A Sullenger
Sep 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rachel L ZemansGregory P Downey
Oct 7, 2011·The Journal of Biological Chemistry·Andrey A KomissarovSteven Idell
Dec 14, 2011·Expert Review of Clinical Immunology·David S PisetskyBruce A Sullenger
Jul 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shashank JainBruce A Sullenger
Aug 2, 2012·The Journal of Clinical Investigation·Michael A MatthayGuy A Zimmerman
Dec 22, 2012·American Journal of Respiratory Cell and Molecular Biology·Livia A VeressCarl W White
Apr 3, 2014·Pediatric Pulmonology·Paul R HouinCarl W White
May 7, 2014·American Journal of Respiratory Cell and Molecular Biology·Raymond C RancourtCarl W White
Jul 22, 2014·Journal of Internal Medicine·H Yanai, T Taniguchi
Jul 26, 2014·Nature Reviews. Immunology·Nicholas J GayClare E Bryant
May 25, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Theodore J Standiford, Peter A Ward
Jun 11, 2016·Annals of the New York Academy of Sciences·Shama Ahmad, Aftab Ahmad
Jul 8, 2016·Annals of the New York Academy of Sciences·Carl W WhiteLivia A Veress
Sep 9, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Cameron S McElroyBrian J Day

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Citations

Jul 1, 2020·Annals of the New York Academy of Sciences·Tapasi RanaAftab Ahmad
Oct 11, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Linsley KellyBruce A Sullenger

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Methods Mentioned

BETA
bronchoalveolar
lavage
bronchoalveolar lavage
ELISA
PCR

Software Mentioned

GraphPad Prism
EPOC
Prism
Vet Blood Analysis System

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