Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid
Open Access
- 1 July 2012
- journal article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 303 (1), L20-L32
- https://doi.org/10.1152/ajplung.00300.2011
Abstract
Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na+-K+-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.Keywords
This publication has 54 references indexed in Scilit:
- Mesenchymal Stem Cells and Acute Lung InjuryCritical Care Clinics, 2011
- Systemic central venous oxygen saturation is associated with clot strength during traumatic hemorrhagic shock: A preclinical observational modelScandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2010
- Tight junctions, but not too tight: fine control of lung permeability by claudinsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injuryAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Recent trends in acute lung injury mortality: 1996–2005*Critical Care Medicine, 2009
- Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endotheliumBioFactors, 2009
- Biology of claudinsAmerican Journal of Physiology-Renal Physiology, 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
- Intra-alveolar tissue factor pathway inhibitor is not sufficient to block tissue factor procoagulant activityAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2008
- Atypical mechanism of NF-κB activation during reoxygenation stress in microvascular endothelium: a role for tyrosine kinasesFree Radical Biology & Medicine, 2002