title: Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury.
abstract: 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.
  
  
  METHODS
  C57BL/6 mice were exposed to lethal lipopolysaccharide doses (10 μg/g of body weight) to induce acute lung injury.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  Wild-type C57BL/6 mice.
  
  
  METHODS
  Ascorbic acid or its oxidized form (dehydroascorbic acid) was administered intraperitoneally at 200 mg/kg 30 mins after the lethal lipopolysaccharide dose.
  
  
  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.affiliation: Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Fisher
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Seropian
authors.forename: Donatas
authors.initials: D
authors.lastname: Kraskauskas
authors.forename: Jay N
authors.initials: JN
authors.lastname: Thakkar
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.forename: Alpha A
authors.initials: AA
authors.lastname: Fowler
authors.forename: Ramesh
authors.initials: R
authors.lastname: Natarajan
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004926:Escherichia coli; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000150:complications / Q000473:pathology / Q000628:therapy
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D001205:Ascorbic Acid