Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS
(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 CITRI...
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MDPI AG
2022-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/20/4415 |
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| author | Xian Qiao Markos G. Kashiouris Michael L’Heureux Bernard J. Fisher Stefan W. Leichtle Jonathon D. Truwit Rahul Nanchal Robert Duncan Hite Peter E. Morris Greg S. Martin Jonathan Sevransky Alpha A. Fowler |
| author_facet | Xian Qiao Markos G. Kashiouris Michael L’Heureux Bernard J. Fisher Stefan W. Leichtle Jonathon D. Truwit Rahul Nanchal Robert Duncan Hite Peter E. Morris Greg S. Martin Jonathan Sevransky Alpha A. Fowler |
| author_sort | Xian Qiao |
| collection | DOAJ |
| description | (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, <i>p</i> = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 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. |
| first_indexed | 2024-03-09T19:38:19Z |
| format | Article |
| id | doaj.art-a6a5972e48574d308f9c6315616c0d29 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T19:38:19Z |
| publishDate | 2022-10-01 |
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| series | Nutrients |
| spelling | doaj.art-a6a5972e48574d308f9c6315616c0d292023-11-24T01:46:27ZengMDPI AGNutrients2072-66432022-10-011420441510.3390/nu14204415Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDSXian Qiao0Markos G. Kashiouris1Michael L’Heureux2Bernard J. Fisher3Stefan W. Leichtle4Jonathon D. Truwit5Rahul Nanchal6Robert Duncan Hite7Peter E. Morris8Greg S. Martin9Jonathan Sevransky10Alpha A. Fowler11Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USADivision of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USADivision of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USADivision of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USADivision of Acute Care Surgical Services, Virginia Commonwealth University, Richmond, VA 23219, USADivision of Pulmonary Disease & Critical Care Medicine, Froedtert and the Medical College of Wisconsin, Aurora St. Luke’s Medical Center, Milwaukee, WI 53215, USADivision of Pulmonary Disease & Critical Care Medicine, Froedtert and the Medical College of Wisconsin, Aurora St. Luke’s Medical Center, Milwaukee, WI 53215, USADivision of Pulmonary Disease & Critical Care Medicine, University of Cincinnati, Cincinnati, OH 45221, USADivision of Pulmonary Disease & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADivision of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USADivision of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USADivision of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA(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, <i>p</i> = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 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.https://www.mdpi.com/2072-6643/14/20/4415sepsisvitamin Cglycocalyxsyndecan-1cell-free DNAacute respiratory distress syndrome |
| spellingShingle | Xian Qiao Markos G. Kashiouris Michael L’Heureux Bernard J. Fisher Stefan W. Leichtle Jonathon D. Truwit Rahul Nanchal Robert Duncan Hite Peter E. Morris Greg S. Martin Jonathan Sevransky Alpha A. Fowler Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS Nutrients sepsis vitamin C glycocalyx syndecan-1 cell-free DNA acute respiratory distress syndrome |
| title | Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS |
| title_full | Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS |
| title_fullStr | Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS |
| title_full_unstemmed | Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS |
| title_short | Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS |
| title_sort | biological effects of intravenous vitamin c on neutrophil extracellular traps and the endothelial glycocalyx in patients with sepsis induced ards |
| topic | sepsis vitamin C glycocalyx syndecan-1 cell-free DNA acute respiratory distress syndrome |
| url | https://www.mdpi.com/2072-6643/14/20/4415 |
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