Document Detail


Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury.
MedLine Citation:
PMID:  21358394     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Sepsis-induced lung injury is a persisting clinical problem with no direct therapy. Recent work suggests that intravenously infused ascorbic acid improves the circulatory dysfunction of sepsis. We used a model of endotoxin-induced acute lung injury to determine whether parenteral ascorbic acid modulates the dysregulated proinflammatory, procoagulant state that leads to lung injury.
DESIGN: C57BL/6 mice were exposed to lethal lipopolysaccharide doses (10 μg/g of body weight) to induce acute lung injury.
SETTING: Laboratory investigation.
SUBJECTS: Wild-type C57BL/6 mice.
INTERVENTIONS: Ascorbic acid or its oxidized form (dehydroascorbic acid) was administered intraperitoneally at 200 mg/kg 30 mins after the lethal lipopolysaccharide dose.
MEASUREMENTS AND MAIN RESULTS: We quantified survival, lung capillary leak, proinflammatory chemokine expression, and lung microvascular thrombosis. Lipopolysaccharide induced 100% lethality in mice within 28 hrs of exposure and in lung we observed intense neutrophil sequestration, loss of capillary barrier function, exuberant pulmonary inflammation, and extensive microthrombus formation. A time-delayed infusion protocol of both ascorbic acid and dehydroascorbic acid significantly prolonged survival. Both ascorbic acid and dehydroascorbic acid preserved lung architecture and barrier function while attenuating proinflammatory chemokine expression and microvascular thrombosis. Ascorbic acid and dehydroascorbic acid attenuated nuclear factor kappa B activation and normalized coagulation parameters.
CONCLUSIONS: Ascorbic acid administered in an interventional manner following lipopolysaccharide infusion attenuates proinflammatory, procoagulant states that induce lung vascular injury in an animal model of sepsis.
Authors:
Bernard J Fisher; Ignacio M Seropian; Donatas Kraskauskas; Jay N Thakkar; Norbert F Voelkel; Alpha A Fowler; Ramesh Natarajan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  39     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-25     Completed Date:  2011-08-11     Revised Date:  2011-09-02    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1454-60     Citation Subset:  AIM; IM    
Affiliation:
Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Lung Injury / drug therapy*,  etiology,  pathology
Animals
Antioxidants / therapeutic use*
Ascorbic Acid / therapeutic use*
Disease Models, Animal
Escherichia coli*
Lipopolysaccharides*
Male
Mice
Mice, Inbred C57BL
Sepsis / complications,  pathology,  therapy
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Lipopolysaccharides; 50-81-7/Ascorbic Acid
Comments/Corrections
Comment In:
Crit Care Med. 2011 Jun;39(6):1590-1   [PMID:  21610641 ]
Erratum In:
Crit Care Med. 2011 Aug;39(8):2022

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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