Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury*
- 1 June 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 39 (6), 1454-1460
- https://doi.org/10.1097/ccm.0b013e3182120cb8
Abstract
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. C57BL/6 mice were exposed to lethal lipopolysaccharide doses (10 μg/g of body weight) to induce acute lung injury. Laboratory investigation. Wild-type C57BL/6 mice. Ascorbic acid or its oxidized form (dehydroascorbic acid) was administered intraperitoneally at 200 mg/kg 30 mins after the lethal lipopolysaccharide dose. 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. 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.This publication has 36 references indexed in Scilit:
- Dehydroascorbic acid as pre-conditioner: Protection from lipopolysaccharide induced mitochondrial damageFree Radical Research, 2010
- Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endotheliumBioFactors, 2009
- Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in miceProceedings of the National Academy of Sciences of the United States of America, 2008
- Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism*Critical Care Medicine, 2008
- Heat Shock Protein 90 Inhibitors Prolong Survival, Attenuate Inflammation, and Reduce Lung Injury in Murine SepsisAmerican Journal of Respiratory and Critical Care Medicine, 2007
- Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular WallCirculation Research, 2007
- Vitamin C fails to protect amino acids and lipids from oxidation during acute inflammationFree Radical Biology & Medicine, 2006
- Nuclear Factor-κB Decoys Suppress Endotoxin-Induced Lung Injury: Fig. 1.Molecular Pharmacology, 2005
- Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase βMolecular and Cellular Biology, 2004
- Coagulopathy of sepsisThrombosis and Haemostasis, 2004