Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS

• Type of Material: Article
• Authors: Xian Qiao, Virginia Commonwealth University; Marks G. Kashiouris, Virginia Commonwealth University; Michael L'Heureux, Virginia Commonwealth University; Bernard J. Fisher, Virginia Commonwealth University; Stefan W. Leichtle, Virginia Commonwealth University; Jonathon D. Truwit, Froedtert and the Medical College of Wisconsin; Rahul Nanchal, Froedtert and the Medical College of Wisconsin; Robert Duncan Hite, University of Cincinnati; Peter E. Morris, University of Alabama Birmingham; Gregory Martin, Emory University; Jonathan Sevransky, Emory University; Alpha A. Fowler, Virginia Commonwealth University
• Language: English
• Date: 2022-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/nu14204415
• Title of Journal or Parent Work: NUTRIENTS
• Volume: 14
• Issue: 20
• Grant/Funding Information: This CITRIS-ALI trial biomarker project was funded by the National Heart Lung and Blood Institute (UM1HL116885); the National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award (CTSA) (UL1TR000058), National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR072000); and the Division of Pulmonary Disease & Critical Care Medicine, VCU School of Medicine.; National Heart: Lung, and Blood Institute: UM1HL116885, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award (CTSA): UL1TR000058, National Institute of Arthritis and Musculoskeletal and Skin Diseases P50AR072000, VCU Investigational Drug Services, McGuff Pharmaceuticals, Santa Ana, CA who supported the trial by supplying the vitamin C with no charges.
• Keywords: SYNDECAN-1; syndecan-1; LUNG INJURY; Life Sciences & Biomedicine; Science & Technology; Nutrition & Dietetics; acute respiratory distress syndrome; MORTALITY; vitamin C; PREDICTOR; sepsis; glycocalyx; ACUTE RESPIRATORY-FAILURE; cell-free DNA
• Research Categories: Health Sciences, Nutrition; Health Sciences, Public Health

Abstract

(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.