| Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. | |
MedLine Citation:
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PMID: 21358394 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Critical care medicine Volume: 39 ISSN: 1530-0293 ISO Abbreviation: Crit. Care Med. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-25 Completed Date: 2011-08-11 Revised Date: 2011-09-02 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1454-60 Citation Subset: AIM; IM |
Affiliation:
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Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Antioxidants; 0/Lipopolysaccharides; 50-81-7/Ascorbic Acid |
| Comments/Corrections | |
Comment In:
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Crit Care Med. 2011 Jun;39(6):1590-1
[PMID:
21610641
]
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Erratum In:
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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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