Citation

Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR, Voelkel NF, Fowler AA, Natarajan R. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012; 303(1): L20-32.

Affiliation

1Virginia Commonwealth University.

Copyright

(Copyright © 2012, American Physiological Society)

DOI

10.1152/ajplung.00300.2011

PMID

22523283

Abstract

Rationale: 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. Objectives: We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Methods: Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 minutes prior to receiving either AscA (200mg/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 anti-coagulants, fibrinolysis mediators) of septic blood. Main Results: 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 pro-inflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance and prevention of sepsis-associated coagulation abnormalities. Conclusions: Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

Language: en